AU2005207882A1

AU2005207882A1 - Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer

Info

Publication number: AU2005207882A1
Application number: AU2005207882A
Authority: AU
Inventors: Pinchas Akiva; Michal Ayalon-Soffer; Dvir Dahary; Alexander Diber; Naomi Keren; Zurit Levine; Amit Novik; Sarah Pollock; Shirley Sameah-Greenwald; Osnat Sella-Tavor; Ronen Shemesh; Maxim Shklar; Rotem Sorek; Amir Toporik; Shira Walach
Original assignee: Compugen USA Inc
Current assignee: Compugen USA Inc
Priority date: 2004-01-27
Filing date: 2005-01-27
Publication date: 2005-08-11
Also published as: WO2005072050A2; CA2554440A1; WO2005072050A9

Description

WO 2005/072050 PCT/IB2005/000433 1 NOVEL NUCLEOTIDE AND AMINO .ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF BREAST CANCER FIELD OF THE INVENTION 5 The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for breast cancer, and assays and methods of use thereof. BACKGROUND OF THE INVENTION Breast cancer is the most commonly occurring cancer in women, comprising almost a 10 third of all malignancies in females. It is the leading cause of death for women between the ages 40-55 in the United States and one out of 8 females in the United States will develop breast cancer at some point in her life. The death rate from breast cancer has been slowly declining over the past decade, partially due do the usage of molecular markers that facilitate the discovery, tumor typing (and 15 therefore choice of treatment), response to treatment and recurrence. The most widely used serum markers for breast cancers are Mucin 1 (measured as CA 15-3) and CEA (CarcinoEmbryonic Antigen). Mucin 1 (MUC ) is present on the apical surface of normal epithelial cells. Its extracellular domain consists of a heavily 0-linked glycosylated peptide core made up of variable number of multiple repeats of 20 amino acid sequence referred 20 to as VNTR (Variable Number Tandem Repeat). This variability results in natural polymorphism of MUCL. Each VNTR has five potential O-linkage sites. The breast cancer disease state alters the enzymes which glycosylate Mucin 1 and therefore the polysaccharide side chains of tumor associated MUC1 are generally shorter than those on the normally expressed molecule. Both aberrant and up-regulated expression of MUC1 are features of 25 malignancy and MUCi related markers are based on it. Though CA 15-3 is a broadly used marker for breast cancer, a combination of CA 15-3 and CEA is more sensitive than using a single marker. For the purpose of monitoring therapeutic response, CA 15-3, CEA and ESR (Erythrocyte Sedimentation Rate) are used as a panel, leading to over 90% of patients 30 biochemically assessable. Serum markers used to monitor therapeutic response in patients with metastatic breast cancer are associated with the "spike phenomenon". It is an initial transient WO 2005/072050 PCT/IB2005/000433 2 rise of tumor marker levels which can be seen in up to 30% of responders in the first 3 months of commencing a therapy. It is important not to interpret this as a sign of disease progression leading to premature change of an effective therapy. CA 27.29 is a new monoclonal antibody directed against a different part of MUC1 and it 5 is a newer n-arker than CA 15-3. It detects a different glycosylation pattern of MUC1, as compared with CA 15-3. CA 27.29 is the first FDA-approved blood test for breast cancer recurrence. Because of superior sensitivity and specificity, CA 27.29 has supplanted CA 15-3 as the preferred tumor marker in breast cancer. The CA 27.29 level is elevated in approximately one third of women with early-stage breast cancer (stage I or II) and in two thirds of women 10 with late-stage disease (stage III or IV). CA 27.29 lacks predictive value in the earliest stages of breast cancer and thus has no role in screening for or diagnosing the malignancy. CA 27.29 also can be found in patients with benign disorders of the breast, liver, and kidney, and in patients with ovarian cysts. However, CA 27.29 levels higher than 100 units per mL are rare in benign conditions. 15 Recently Estrogen 2 (beta) was shown to have a diagnostic role in breast cancer. It has been shown that the expression of the 'cx' variant of Estrogen 2 is correlated with response to Hormone adjuvant therapy. In addition it has been shown it may assist in better characterization of ER-I positive breast cancers (together with progesterone receptor). HER-2 (also known as c-erbB2) is a membrane proto-oncogene with intrinsic tyrosine 20 kinase activity. Tumor expressing HER-2 are associated with shorter survival, shorter time-to relapse and an -overall worse prognosis. Tumors expressing HER-2 can be targeted with Trastuzumab - a biological adjuvant therapy which blocks the growth promoting action of HER 2. The ImmunoHistoChemistry (IHC) and Fluorescence In Situ Hybridization (FISH) tests are used to detect HER2: 1.IHC: The most common test used to check HER2 status is an 25 ImmunoHistoChemistry (IHC) test. The IHC test measures the protein made by the HER2 gene. 2. FISH: This test measures the number of copies of the HER2 gene present in the tumor cell. Measurement of the extracellular domain of HER-2 has been reported to show a better assessment of response to chemotherapy than a biochemical index score based on measurement of CA 15.3, CEA and ESR in a small series of patient. That finding is yet to be confirmed in a 30 larger group of patient with HER-2 expressing tumors.

WO 2005/072050 PCT/IB2005/000433 3 Other molecular markers, mainly used for the diagnosis for cancers other than breast cancer were shown to have a diagnostic potential in breast cancer. For example, CA125 which is a major marker for ovarian cancer is also associated with breast cancer. High levels of CA 19-9, a major marker for colorectal and pancreatic cancers, can be found in breast cancer. Overall, 5 these markers are not frequently used for the detection of breast cancer to due their inferiority compared with other markers already described. Panels of markers for the diagnosis and typing of breast cancer are being used by pathologists, including both markers described above and additional markers, such as immunohistochemistry markers that have been shown to have a beneficial value for the 10 diagnosis of breast cancer, including PCNA and Ki-67 are maybe the most important and highly used immunohistochemistry markers for breast cancer. Other markers as E-Cadherin, Cathepsin D and TFF1 are also used for that purpose. Despite relevant research efforts and the identification of many putative good prognosticators, few of them are proving clinically useful for identifying patients at minimal risk 15 of relapse, patients with a worse prognosis, or patients likely to benefit from specific treatments. Most of them, such as epidermal growth factor receptor, cyclin E, p53 (this mutation is present in approximately 40% of human breast cancers as an acquired defect), bcl-2, vascular endothelial growth factor, urokinase-type plasminogen activator- 1 and the anti-apoptosis protein survivin, are suggested for possible inclusion in the category of biomarkers with a high level of 20 clinico-laboratory effectiveness. However, no single biomarker was able to identify those patients with the best (or worst) prognosis or those patients who would be responsive to a given therapy. High level cycin E expression has been associated with the initiation or progression of different human cancers, in particular breast cancer but also leukemia, lymphoma and others. Cyclin-E expression level in the breast cancer was found to be a very strong indicator for 25 prognosis, stronger than any other biological marker. There are some non-cancerous pathological conditions which represent an increased risk factor for development breast cancer. Non-limiting examples of these conditions include: - Ductal hyperplasia without atypia. It is the most frequently encountered breast biopsy result that is associated with increased risk of future development of breast cancer (2 fold 30 increased risk). In particular, the loss of expression of transforming growth factor beta WO 2005/072050 PCT/IB2005/000433 4 receptor II in the affected epithelial cells is associated with an increased risk of invasive breast cancer. - Atypical hyperplasia. Women having atypical hyperplasia with over-expression of HER-2 have a greater than 7-fold increased risk of developing invasive breast 5 carcinoma, as compared with women with non-proliferative benign breast lesions and no evidence of HER-2 amplification. These pathological conditions should be effectively diagnosed and monitored in order to facilitate early detection of breast cancer. .10 SUMMARY OF THE INVENTION The background art does not teach or suggest markers for breast cancer that are sufficiently sensitive and/or accurate, alone or in combination. The present invention overcomes these deficiencies of the background art by providing novel markers for breast cancer that are both sensitive and accurate. These markers are 15 overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient (biological) samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states. 20 According to preferred embodiments of the present invention, examples of suitable biological samples which may optionally be used with preferred embodiments of the present invention include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, breast tissue, any human organ or tissue, 25 including any tumor or normal tissue, any sample obtained by lavage (for example of the bronchial system or of the breast ductal system), and also samples of in vivo cell culture constituents. In a preferred embodiment, the biological sample comprises breast tissue and/or a serum sample and/or a urine sample and/or a milk sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable eluant before contacting the sample 30 to an antibody and/or performing any other diagnostic assay.

WO 2005/072050 PCT/IB2005/000433 5 Information given in the text with regard to cellular localization was determined according to four different software programs: (i) tmhmm (from Center for Biological Sequence Analysis, Technical University of Denmark DTU, 5 http://www.cbs.dtu.dk/services/TMHMM/TMHIMM2.0b.guide.php) or (ii) tmpred (from EMBnet, maintained by the ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Institute of Bioinformatics, http://www.ch.embnet.org/software/TMPRED-form.html) for transmembrane region prediction; (iii) signalpjhmm or (iv) signalpnn (both from Center for Biological Sequence 10 Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/SignalP/background/prediction.php) for signal peptide prediction. The terms "signalp-hmm" and "signalp-nn" refer to two modes of operation for the program SignalP: hmm refers to Hidden Markov Model, while nn refers to neural networks. Localization was also determined through manual inspection of known protein localization 15 and/or gene structure, and the use of heuristics by the individual inventor. In some cases for the manual inspection of cellular localization prediction inventors used the ProLoc computational platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) "Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis." Cell Biology 20 International 2004;28(3):171-8.], which predicts protein localization based on various parameters including, protein domains (e.g., prediction of trans-membranous regions and localization thereof within the protein), pI, protein length, amino acid composition, homology to pre-annotated proteins, recognition of sequence patterns which direct the protein to a certain organelle (such as, nuclear localization signal, NLS, mitochondria localization signal), signal 25 peptide and anchor modeling and using unique domains from Pfam that are specific to a single compartment. Information is given in the text with regard to SNPs (single nucleotide polymorphisms). A description of the abbreviations is as follows. "T - > C", for example, means that the SNP results in a change at the position given in the table from T to C. Similarly, "M - > Q", for 30 example, means that the SNP has caused a change in the corresponding amino acid sequence, from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the WO 2005/072050 PCT/IB2005/000433 6 nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*). As part of the description of an SNP, a comment may be found in parentheses after the above description of the SNP itself. This comment may include an FTId, 5 which is an identifier to a SwissProt entry that was created with the indicated SNP. An FTId is a unique and stable feature identifier, which allows construction of links directly from position specific annotation in the feature table to specialized protein-related databases. The FTId is always the last component of a feature in the description field, as follows: FTId=XXXnumber, in which XXX is the 3-letter code for the specific feature key, separated by an underscore from 10 a 6-digit number. In the table of the amino acid mutations of the wild type proteins of the selected splice variants of the invention, the header of the first column is "SNP position(s) on amino acid sequence", representing a position of a known mutation on amino acid sequence. SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker. Preferred 15 embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein. Information given in the text with regard to the Homology to the known proteins was 20 determined by Smith-Waterman version 5.1.2 using special (non default) parameters as follows: -model=sw.model -GAPEXT=O -GAPOP=100.0 -MATRIX=blosum100 25 Information is given with regard to overexpression of a cluster in cancer based on ESTs. A key to the p values with regard to the analysis of such overexpression is as follows: - library-based statistics: P-value without including the level of expression in cell lines (PI) - library based statistics: P-value including the level of expression in cell-lines (P2) 30 - EST clone statistics: P-value without including the level of expression in cell- lines (SP1) WO 2005/072050 PCT/IB2005/000433 7 - EST clone statistics: predicted overexpression ratio without including the level of expression in cell-lines (R3) - EST clone statistics: P-value including the level of expression in cell-lines (SP2) - EST clone statistics: predicted overexpression ratio including the level of 5 expression in cell-lines (R4) Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer. Information is given with regard to overexpression of a cluster in cancer based on 10 microarrays. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. There are two types of microarray results: those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from 15 microarrays using Affymetrix technology. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. For microarrays prepared according to a design by the present inventors, the probe name begins with the name of the cluster (gene), followed by an identifying number. Oligonucleotide microarray results taken from Affymetrix data were from chips 20 available from Affymetrix Inc, Santa Clara, CA, USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymetrix.com/products/arrays/specific/hgul33.affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33av2.affx; and Human Genome U133 Plus 2.0 Array at 25 www.affymetrix.com/products/arrays/specific/hgul33plus.affx). The probe names follow the Affymetrix naming convention. The data is available from NCBI Gene Expression Omnibus (see www.ncbi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1 207-2 10). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/ace.cgi?acc=GSE 1133 for the Series GSE 1133 database 30 (published on March 2004); a reference to these results is as follows: Su et al (Proc Nati Acad WO 2005/072050 PCT/IB2005/000433 8 Sci U S A. 2004 Apr 20;101(16):6062-7. Epub 2004 Apr 09). The probes designed according to the present inventors are listed below. >Z21368_0_0_61857 (SEQ ID NO:895) AGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACTCTTGAAG 5 >HUMGRP5E_0-0_16630 (SEQ ID NO:896) GCTGATATGGAAGTTGGGGAATCTGAATTGCCAGAGAATCTTGGGAAGAG >HUMGRP5E_20 (SEQ ID NO:897) TCTCATAGAAGCAAAGGAGAACAGAAACCACCAGCCACCTCAACCCAAGG >HSENA78_0_1_0 (SEQ ID NO:898) 10 TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC >M854910 025999 (SEQ ID NO:899) GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC >M854910140 (SEQ ID NO:900) GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG 15 >HSSTROL3_0_0_12518 (SEQ ID NO: 901) ATGAGAGTAACCTCACCCGTGCACTAGTTTACAGAGCATTCACTGCCCCA >HSSTROL3_0_0_12517 (SEQ ID NO:902) CAGAGATGAGAGCCTGGAGCATTGCAGATGCCAGGGACTTCACAAATGAA >HUMCAIXIA_0_0_14909 (SEQ ID NO:903) 20 GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG >HUMCA IXIA_0_18_0 (SEQ ID NO:904) TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG >R20779_0_0_30670 (SEQ ID NO:905) CCGCGTTGCTTCTAGAGGCTGAATGCCTTTCAAATGGAGAAGGCTTCCAT 25 >HSS100PCB_0_0_12280 (SEQ ID NO:906) CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA >HSCOC4_0_0_9892 (SEQ ID NO:907) AAGGACCAGAGTCCATGCCAAGACCACCCTTCAGCTTCCAAGGCCCTCCA >HSCOC4_0_390 (SEQ ID NO:908) 30 ATCCTCCAGCCATGAGGCTGCTCTGGGGGCTGATCTGGGCATCCAGCTTC >HSCOC4_0_0_9883 (SEQ ID NO:909) WO 2005/072050 PCT/IB2005/000433 9 CCTGTTTGCTCTGACACCAACTTCCTACCCTCTCAGCCTCAAAGT A CTC >HSCOC4_0_0_9885 (SEQ ID NO:910) GCTGAGGTGTGGCCGAGGACCTGACCATCTGGAAGTGTGAAAATCCCCTT >T11628_0_9_0 (SEQ ID NO:911) 5 ACAAGATCCCCGTGAAGTACCTGGAGTTCATCTCGGAATGCATCATCCAG >T11628_0_0_45174 (SEQ ID NO:912) TAAACAATCAAAGAGCATGTTGGCCTGGTCCTTTGCTAGGTACTGTAGAG >T11628_00_45161 (SEQ ID NO:913) TGCCTCGCCACAATGGCACCTGCCCTAAAATAGCTTCCCATGTGAGGGCT 10 >M78076_0_7_0 (SEQ ID NO:914) GAGAAGATGAACCCGCTGGAACAGTATGAGCGAAAGGTGAATGCGTCTGT >HSMUC1A_0_37_0 (SEQ ID NO:915) AAAAGGAGACTTCGGCTACCCAGAGAAGTTCAGTGCCCAGCTCTACTGAG >HSMUCI A__0_11364 (SEQ ID NO:916) 15 AAAGGCTGGCATAGGGGGAGGTTTCCCAGGTAGAAGAAGAAGTGTCAGCA >HSMUC1A_0_0_11365 (SEQ ID NO:917) AATTAACCCTTTGAGAGCTGGCCAGGACTCTGGACTGATTACCCCAGCCT The following list of abbreviations for tissues was used in the TAA histograms. The term 20 "TAA" stands for "Tumor Associated Antigen", and the TAA histograms, given in the text, represent the cancerous tissue expression pattern as predicted by the biomarkers selection engine, as described in detail in examples 1-5 below. "BONE" for "bone"; "COL" for "colon"; 25 "EPI" for "epithelial"; "GEN" for "general"; "LIVER" for "liver"; "LUN" for "lung"; "LYMPH" for "lymph nodes"; 30 "MARROW" for "bone marrow"; "OVA" for "ovary"; WO 2005/072050 PCT/IB2005/000433 10 "PANCREAS" for "pancreas"; "PRO" for "prostate"; "STOMACH" for "stomach"; "TCELL" for "T cells"; 5 "THYROID" for "Thyroid"; "MAM" for "breast"; "BRAIN" for "brain"; "UTERUS" for "uterus"; "SKIN" for "skin"; 10 "KIDNEY" for "kidney"; "MUSCLE" for "muscle"; "ADREN" for "adrenal"; "HEAD" for "head and neck"; "BLADDER" for "bladder"; 15 It should be noted that the terms "segment", "seg" and "node" are used interchangeably in reference to nucleic acid sequences of the present invention, they refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid seqences as 20 described in greater detail below. Optionally and preferably, they are examples of oligonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use. As used herein the phrase "breast cancer" refers to cancers of the breast or surrounding 25 tissue, including but not limited to ductal carcinoma (in-situ or invasive), lobular carcinoma (in situ or invasive), inflammatory breast cancer, mucinous carcinoma, tubular carcinoma, or Paget's disease of the nipple, as well as conditions that are indicative of a higher risk factor for later development of breast cancer, including but not limited to ductal hyperplasia without atypia and atypical hyperplasia, referred to herein collectively as "indicative conditions". 30 The term "marker" in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from WO 2005/072050 PCT/IB2005/000433 11 subjects (patients) having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from subjects who do not have breast cancer (or one of the above indicative conditions). The phrase "differentially present" refers to differences in the quantity of a marker 5 present in a sample taken from patients having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from patients who do not have breast cancer (or one of the above indicative conditions). For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in 10 the other sample, for example as measured by hybridization and/or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present. 15 As used herein the phrase "diagnostic" means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The "sensitivity" of a diagnostic assay is the percentage of diseased individuals who test positive (percent of "true positives"). Diseased individuals not detected by the assay are "false negatives." Subjects who are not diseased and who test negative in the assay are termed "true 20 negatives." The "specificity" of a diagnostic assay is I minus the false positive rate, where the "false positive" rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis. As used herein the phrase "diagnosing" refers to classifying a disease or a symptom, 25 determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term "detecting" may also optionally encompass any of the above. Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample 30 obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a "biological sample obtained from WO 2005/072050 PCT/IB2005/000433 12 the subject" may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below. As used herein, the term "level" refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention. 5 Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample obtained from a healthy individual (examples of biological samples are described herein). Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or 10 polypeptide of the variant of interest in the subject. Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made. 15 Determining the level of the same variant in normal tissues of the same origin is preferably effected along-side to detect an elevated expression and/or amplification and/or a decreased expression, of the variant as opposed to the normal tissues. A "test amount" of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of breast cancer (or one of the above indicative conditions). A test 20 amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). A "control amount" of a marker can be any amount or a range of amounts to be compared against a test amount of a marker. For example, a control amount of a marker can be the amount of a marker in a patient with breast cancer (or one of the above indicative 25 conditions) or a person without breast cancer (or one of the above indicative conditions). A control amount can be either in absolute amount (e.g., microgram/mi) or a relative amount (e.g., relative intensity of signals). "Detect" refers to identifying the presence, absence or amount of the object to be detected. 30 A "label" includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means. For example, useful labels include 32 P, 35 s, WO 2005/072050 PCT/IB2005/000433 13 fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules with a sequence complementary to a target. The label often generates a measurable signal, such as a radioactive, chromogenic, or 5 fluorescent signal, that can be used to quantify the amount of bound label in a sample. The label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated nucleotides that are recognized by streptavadin. The label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly 10 or indirectly. For example, the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequere, which is the binding partner for a complementary sequence, to which it can specifically hybridize. The binding partner may itself be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule. The binding partner also may be indirectly detectable, for example, a nucleic acid 15 having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry. Exemplary detectable labels, optionally and preferably for use with immunoassays, 20 include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay 25 wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture. "Immunoassay" is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen. 30 The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," when referring to a protein or peptide (or other epitope), WO 2005/072050 PCT/IB2005/000433 14 refers to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other 5 proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic 10 variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A 15 Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background. According to preferred embodiments of the present invention, there is provided an 20 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TranscriptNme_ T10888-PEA_1_T4 T10888_PEAl_T4 T1088S-PEA_1_T5 T10888PEA_1_T6 a nucleic acid sequence comprising a sequence in the table below: Segment Name T10888_PEA_1_node 11 WO 2005/072050 PCT/IB2005/000433 T10888-PEA_ _node-12 T10888_PEA_1_node_17 T10888_PEA_1-node_4 T10888-PEA_1_node_6 T10888_PEA-1_node_7 T10888_PEAInode_9 T10888-PEA_1_node_15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below amino acid sequence comprising a sequence in the table below: T10888_PEA_1_P2 T10888_PEA_1_P4 T10888_PEA_1_P5 T10888_PEA_1_P6 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name T39971-TIO T39971_T12 T39971_T16 T39971_T5 a nucleic acid sequence comprising a sequence in the table below: Segment Name T39971_node_0 T39971_node_18 T39971_node_21 WO 2005/072050 PCT/IB2005/000433 16 T39971_rode_22 T39971 r:,ode_23 T39971.node_31 T39971_node_33 T39971_node_7 T39971_node_1 T39971_node_10 T39971_node_11 T39971_node_12 T39971_node_15 T39971_node_16 T39971_node_17 T39971_node_26 T39971_node_27 T39971_node_28 T39971_node_29 T39971_node_3 T39971_node_30 T39971_node_34 T39971_node_35 T39971_node_36 T39971_node_4 T39971_node_5 T39971_node_8 T39971_node_9 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: Protein Name WO 2005/072050 PCT/IB2005/000433 17 T39971_P6 T39971_P9 T39971 P11 T39971_P12 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprisinga nuileic acid sequence in the table below and/or: Transcript Name Z21368_PEA_1_T10 Z21368_PEA_1 TiI Z21368-PEA_1_T23 Z21368_PEA_1_T24 Z21368_PEAI T5 Z21368_PEA_1_T6 Z21368_PEA_1_T9 a nucleic acid sequence comprising a sequence in the table below: Segment Name Z21368_PEA_1_node_0 Z21368_PEA_1_node 15 Z21368_PEA 1 node_19 Z21368_PEAInode_2 Z21368_PEA_1_node_21 721368_PEAInode 33 Z21368_PEA 1_node_36 Z21368_PEA_1_node_37 Z21368_PEAInode_39 Z21368_PEAInode_4 Z21368_PEA_1_node 41 Z21368_PEAInode_43 WO 2005/072050 PCT/IB2005/000433 18 Z21368_PEA_1node_45 Z21368_PEA_1_node_53 Z21368_PEA_1node-56 g 38_EA_1 node_58 Z2168 PEA _node-66 Z21368_PEAInode_67 Z21368_PEA_1_node_69 Z21368_PEA 1_node 11 Z21368_PEA_1 node_12 Z21368_PEA_1_node_16 Z21368_PEA_1 node_17 Z21368_PEA_1 node 23 Z21368_PEA_1 node_24 Z21368_PEA_1_node_30 Z21368_PEA1node_31 Z21368_PEA_1_node_38 Z21368_PEA1_node_47 Z21368_PEAInode 49 Z21368_PEA1node_51 Z21368_PEA_1node61 Z21368_PEAInode_68 Z21368_PEAInode_7 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name Z21368_PEA1._P2 Z21368_PEA_1-P5 Z21368_PEA_1-P15 WO 2005/072050 PCT/IB2005/000433 19 Z21368PEA1 PI6 Z21368_PEA_1_P22 Z21368_PEA_1_P23 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name T59832_Tll T59832_T15 T59832 T22 T59832_T28 T59832_T6 T59832_T8 a nucleic acid sequence comprising a sequence in the table below: Segment Name T59832_nodeI T59832_node_22 T59832_node_23 T59832_node_24 T59832_node_29 T59832_node_39 T59832_node_7 T59832-node_10 T59832_node_11 T59832_node_12 T59832-node_14 T59832_node_16 T59832_node_19 T59832_node_2 T59832_node_20 WO 2005/072050 PCT/IB2005/000433 20 T59832_node_25 T59832_node 26 T59832_node_27 T59832_node_28 T59832_node_3 T59832_node_30 T59832_node-31 T59832_node_32 T59832_node_34 T59832_node_35 T59832_node_36 T59832_node_37 T59832_node_38 T59832-node_4 T59832_node_5 T59832_node-6 T59832_node_8 T59832_node_9 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name T59832_P5 T59832_P7 T59832_P9 T59832_P12 T59832_P18 According to preferred embodiments of the present invention, there is provided an 5 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: WO 2005/072050 PCT/IB2005/000433 2 1 Transcript Name Z41644_PEA_1_T5 a nucleic acid sequence comprising a sequence in the table below: Segment Name Z41644-PEA.1_node_0 Z41644_PEAInode_1l Z41644_PEA_1 node_12 Z41644_PEA 1 node_15 Z41644_PEA_1_node_20 Z41644-PEA_1_node_24 Z41644_PEA_-node_1 Z41644-PEAInode 10 Z41644_PEAInode 13 Z41644-PEAInode 16 Z41644_PEA-_node 17 Z41644-PEA._1_node 19 Z41644_PEA-_node 2 Z41644_PEA_1_node 21 Z41644_PEA_1_node_22 Z41644_PEA_1_node_23 Z41644_PEA_1_node 25 Z41644_PEA_1_node 3 Z41644_PEA_1_node_4 Z41644_PEAInode_6 Z41644_PEA_1 node_9 According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide comprising an amino acid sequence in the table below WO 2005/072050 PCT/IB2005/000433 2 2 Protein Name Z41644_PEAI_P10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Namg HUTMGRP5E T4 HULMGRP5E T5 5 a nucleic acid sequence comprising a sequence in the table below: Segment Name H-UMGRP5E node_0 HUMGRP5E node_2 HIUMGRP5E node 8 HUMGRP5E node 3 HLJMGRP5E node_7 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HUMGRP5EP4 HUMGRP5EP5 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name AA155578_PEA_1TIO WO 2005/072050 PCT/IB2005/000433 23 AA155578 PEA_1_T12 AA155578_PEA_1_T13 AA155578_PEA_1_T8 a nucleic acid sequence comprising a sequence in the table below: Segment Name AA155578_PEA I node 11 AA155578_PEA I node 12 AA155578_PEA I node 14 AA155578_PEA 1 node 19 AA155578_PEA 1 node_21 AA155578_PEA 1 node_23 AA155578_PEA Inode_24 AA 155578_PEA_ 1 node_25 AA155578_PEAInode_4 AA155578_PEA_1 node_7 AA155578-PEA 1node 15 AA155578_PEAI node 18 AA155578-PEA 1_node 22 AA155578_PEA_1_node_6 AA155578_PEA1 node_8 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name AA155578_PEA1 _P4 AA155578_PEA_1_P6 AA155578_PEA1 1P8 AA155578_PEA 1 P9 WO 2005/072050 PCT/IB2005/000433 24 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HSENA7S._T5 a nucleic acid sequence comprising a sequence in the table below: Segment Name HSENA78_node_0 HSENA78node 2 HSENA78_node_6 HSENA78_node 9 HSENA78_node_3 HSENA78_node_4 HSENA78_nodeS 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: Protein Name HSENA78_P2 According to preferred embodiments of the present invention, there is provided an 10 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name T94936_PEA_1_TI T94936_PEA_1_T2 a nucleic acid sequence comprising a sequence in the table below: Segment Name WO 2005/072050 PCT/IB2005/000433 25 T94936_PEA I node 14 T94936_PEA_1 node_16 T94936-PEA_1node_2 T94936_PEA_1_node_20 T94936-PEA_1_node_23 T94936_PEA_1 node_0 T94936_PEA1 node-I T94936_PEA_1_node_13 T94936_PEA_1 node 17 T94936_PEA_1node_6 T94936_PEA_1 node 8 T94936_PEA_1_node 9 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name T94936_PEAl-P2 T94936_PEA_1_P3 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name M85491_PEA_1_T16 M85491_PEA_1_T20 a nucleic acid sequence comprising a sequence in the table below: Segment Name M85491_PEA_1_node_0 WO 2005/072050 PCT/IB2005/000433 26 M85491_PEA_1 node_13 M85491_PEA_1_node 21 M85491_PEA_1_node_23 M85491_PEAInode_24 M85491-PEAInode_8 M85491_PEA_1 node_9 M85491_PEA_1_node_10 M85491_PEA_1_node_18 M85491_PEA_1_node_19 M85491-PEA_1_node_6 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name M85491_PEA_1_P13 M85491_PEA1_-P14 According to preferred embodiments of the present invention, there is provided an 5 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TranscriptName HSSTROL3 T5 HSSTROL3_T8 HSSTROL3_T9 HSSTROL3_T1O HSSTROL3_Ti 1 HSSTROL3_T12 a nucleic acid sequence comprising a sequence in the table below: Segment Name HSSTROL3_node_6 WO 2005/072050 PCT/IB2005/000433 27 HSSTROL3_node 10 HSSTROL3-node_13 HSSTROL3_node_15 HSSTROL3_node_19 HSSTROL3_node_21 HSSTROL3_node 24 HSSTROL3_node_25 HSSTROL3_node_26 HSSTROL3_node_28 HSSTROL3_node 29 HSSTROL3_nodell HSSTROL3_node_17 HSSTROL3_node_18 HSSTROL3-node_20 HSSTROL3-node_27 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HSSTROL3_P4 HSSTROL3_P5 HSSTROL3_P7 HSSTROL3_PS HSSTROL3_P9 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name AY180924_PEA_1_TI WO 2005/072050 PCT/IB2005/000433 28 a nucleic acid sequence comprising a sequence in the table below: Segment Name AY180924_PEA_1_node_3 AY 180924_PEA Inode_0 AY180924-PEA- _Inode_2 According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide comprising an amino acid sequence in the table below Protein Name AY180924_PEAlP3 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name R75793_PEA-1-TI R75793-PEAlT3 R75793_PEA_1_T5 10 a nucleic acid sequence comprising a sequence in the table below: R75793_PEA_1_node_0 R75793-PEA_1_node_9 R75793_PEA 1 node- I R75793_PEA_1_node_14 R75793_PEA_1_node_4 R75793_PEA_1_node_5 R75793_PEAInode_6 R75793_PEA_1_node_8 WO 2005/072050 PCT/IB2005/000433 29 R75793_PEA_1_node_13 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name R75793_PEA_1_P2 R75793_PEA_1_P5 R75793_PEA__P6 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HUMCAIXIA-T16 HLMCA IXIAT 17 HUMCAlXIA-TI 19 HUMCA 1XIAT20 a nucleic acid sequence comprising a sequence in the table below: Segment Name HUMCA1XIAnode_0 HUMCAIXIA-node_2 HIUMCAXIA-node_4 HUMCA1XIA-node_6 HUMCAIXIA-node-8 HIUMCA1XIAnode_9 HJMCA1XIA_node_18 HUMCAlXIA-node_54 HUMCA1XIA-node_55 WO 2005/072050 PCT/IB2005/000433 30 HUMCAIXIA node_92 HUMCAIXIAnode_ 11 HUMCAIXIAnode_15 HUMCAIXIA node_19 HJMCAIXIAnode_21 H-UMCAIXIA_node_23 LUMCAIXIAnode_25 HUMCAIXIAnode_27 HUJMCA1XIA_node_29 HIUMCA1XIA-node_31 H-UMCAIXIAnode_33 H-UMCA1XIAnode_35 HJMCAIXIA node_37 HUMCA1XIAnode_39 LIUMCAIXIAnode_41 HUMCA1XIAnode_43 HUMCA1XIA node 45 HUMCAlXIAnode_47 HUMCA1XIA node-49 HUMCA1XIAnode_51 HUIMCAIXIA-node_57 HUMTNCA IXIA-node._S9 H-UMCA1XIAnode_62 HUMCAIXIAnode_64 HUJMCAIXIA-node._66 HUM~vCAIXIA-node-68 HUMCAl'XIA-node-70 HUMCAIXIAnode_72 HUMCAIXIAnode_74 -JUMCAXIAnode_76 WO 2005/072050 PCT/IB2005/000433 31 HU-LMCAlXIA node_78 HUMCA1XIA node_81 HUMCA I XIA node 83 HUMCA1XIA node 85 HULTMCAIXIA node_87 HJMCAIXIA node 89 HUMCAIXIA node_91 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HUMCA1XIA P14 HUMCA1XIA P15 HUMCA1XIAP16 H-UMCA1XIAP17 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name R20779_T7 a nucleic acid sequence comprising a sequence in the table below: Segment Name R20779_node_0 R20779-node_2 R20779_node_7 R20779_node_9 R20779_node_18 R20779_node_21 WO 2005/072050 PCT/IB2005/000433 32 R20779_node-24 R20779_node 27 R20779_node_28 R20779_node 30 R20779_node-31 R20779_node_32 R20779_nodeI R20779_node_3 R20779_node_10 R20779_node_11 R20779_node_14 R20779_node_17 R20779_node_19 R20779_node_20 R20779-node_22 R20779_node_23 R20779-node_25 R20779-node_29 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to R20779_P2. According to preferred embodiments of the present invention, there is provided an 5 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HSS100PCB_T1 a nucleic acid sequence comprising a sequence in the table below: Segment Name HSSIOOPCBnode_3 WO 2005/072050 PCT/IB2005/000433 33 HSS100PCB node_4 HSS100PCB_node_5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to HSS100PCBP3. According to preferred embodiments of the present invention, there is provided an 5 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TranscriptName HSCOC4_PEA_1_TI HSCOC4_PEA__T2 HSCOC4_PEA_1_T3 HSCOC4_PEA_1 T4 HSCOC4_PEA_T5 HSCOC4_PEA_1_T7 HSCOC4_PEA_T8 HSCOC4_PEAI _Ti 1 HSCOC4_PEA_1 T12 HSCOC4_PEA1 _T14 HSCOC4_PEA_1_TI5 HSCOC4_PEAI _T20 HSCOC4_PEA_T21 HSCOC4_PEAIT25 HSCOC4_PEA_T28 HSCOC4_PEAIT30 HSCOC4_PEA_1_T31 HSCOC4_PEAIT32 HSCOC4_PEA_1_T40 a nucleic acid sequence comprising a sequence in the table below: WO 2005/072050 PCT/IB2005/000433 34 Segment Name HSCOC4-PEA_1_node_1 HSCOC4_PEA_1_node_5 HSCOC4-PEA_1_node_7 HSCOC4_PEA_1_node_30 HSCOC4_PEA_1_node-33 HSCOC4_PEAI 1node_35 HSCOC4_PEA 1_node_37 HSCOC4-PEAI lnode_39 HSCOC4_PEAInode_43 HSCOC4_PEA_1 node_48 HSCOC4_PEA_1_node_49 HSCOC4-PEA_1 node_51 HSCOC4_PEA_1 node_58 HSCOC4_PEA_1_node_59 HSCOC4_PEA 1 node_62 HSCOC4-PEA_1 node_66 HSCOC4_PEA_1_node_72 HSCOC4_PEAInode-77 HSCOC4_PEA_1_node_79 HSCOC4_PEA_1_node_93 HSCOC4_PEA 1 node 100 HSCOC4_PEA_1_node_105 HSCOC4_PEAInode-107 HSCOC4 PEA 1 node 108 HSCOC4 PEA- 1 node- 109 HS COC4_PEA- I-node- I 10 HSCOC4_PEAInode_113 HSCOC4_PEA_1_node_2 WO 2005/072050 PCT/IB2005/000433 35 HSCOC4_PEAI lnode_8 HSCOC4-PEA1 -node_10 HSCOC4_PEA_1_node_12 HSCOC4_PEA1 -node 14 HSCOC4-PEA 1 node 17 HSCOC4_PEA I node 19 HSCOC4-PEA 1-node_21 HSCOC4_PEA_1-node_22 HSCOC4_PEA_1_node_28 HSCOC4-PEA_1_node_29 HSCOC4_PEA-1 node_41 HSCOC4_PEA-_1node_45 HSCOC4-PEA_1_node_47 HSCOC4_PEA_-node_50 HSCOC4-PEA1_-node_53 HSCOC4_PEA_-node_55 HSCOC4_PEA 1 node_57 HSCOC4_PEA-_node_60 HSCOC4_PEA_1_node-64 HSCOC4_PEA_1_node_69 HSCOC4_PEA_1_node_70 HSCOC4_PEA_1 node_71 HSCOC4_PEA_1 node_73 HSCOC4_PEA_1_node_74 HSCOC4_PEA_1_node_75 HSCOC4-PEA_1_node_76 HSCOC4-PEA_1_node-78 HSCOC4_PEA_1_node_80 HSCOC4_PEA-_node_82 HSCOC4_PEA_-node_83 WO 2005/072050 PCT/IB2005/000433 36 HSCOC4_PEA_1_node_84 HSCOC4_PEA_1_node_85 HSCOC4_PEA_1_node_86 HSCOC4_PEA 1 node 87 HSCOC4_PEA_1 node 88 HSCOC4_PEAI node 89 HSCOC4_PEA_1_node 90 HSCOC4_PEA I node 91 HSCOC4_PEA_1_node_92 HSCOC4_PEA_1 node_94 HSCOC4_PEA 1 node 96 HSCOC4_PEA 1 node 97 HSCOC4_PEA 1 node 98 HSCOC4_PEA_1 node_99 HSCOC4_PEA_1 node 101 HSCOC4_PEA 1 node 102 HSCOC4_PEA 1 node 103 HSCOC4_PEA 1 node 104 HSCOC4_PEA_1 node 106 HSCOC4_PEA I node 111 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HSCOC4_PEA_1_P3 HSCOC4_PEA_-P5 HSCOC4_PEA_1 P6 HSCOC4_PEA 1 P12 HSCOC4_PEA_1 P15 HSCOC4_PEA_1_P16 WO 2005/072050 PCT/IB2005/000433 37 HSCOC4-PEA_1_P20 HSCOC4-PEAl-P9 HSCOC4-PEA__P22 HSCOC4-PEA_1_P23 HSCOC4-PEA_-P24 HSCOC4_PEA 1_P25 HSCOC4_PEA_1 P26 HSCOC4_PEA 1 P30 HSCOC4_PEA 1 P38 HSCOC4_PEA_1_P39 HSCOC4_PEA 1 P40 HSCOC4_PEA 1 P41 HSCOC4_PEA 1 P42 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HUMTREFACPEA 2 T4 HUMTREFAC PEA 2 T5 5 a nucleic acid sequence comprising a sequence in the table below: Segment Name HUMTREFACPEA 2 node_0 HUMTREFACPEA 2 node_9 HUMTREFAC PEA 2 node_2 HUMTREFACPEA_2_node_3 HUMTREFACPEA 2 node_4 HUMTREFACPEA_2 node_5 HUMTREFACPEA_2_node_8 WO 2005/072050 PCT/IB2005/000433 38 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HUMTREFACPEA_2P7 HUMTREFACPEA_2JPS 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HUMOSTRO-PEA-1-PEA_1_T14 HUJMOSTROPEA-_1PEA_1_T16 HUMOSTROPEA_1_PEA_1_T30 a nucleic acid sequence comprising a sequence in the table below: Segment Name HUMOSTROPEA_ 1PEA_1 node_0 HUMOSTROPEA_ 1PEA 1 node_10 HUMOSTROPEA_1 PEA 1 node 16 HUMOSTROPEA_ _PEAInode_23 HUMOSTROPEA_1 PEA_1_node_31 HJMOSTROPEA_1 PEA_1_node_43 HUJMOSTRO-PEA_1_PEA_1node_3 HUMOSTRO-PEA1 _PEA_1 node_5 HUMOSTROPEA1__PEA_1-node_7 HUJMOSTROPEAI _PEA_1_node_8 HUMOSTROPEA- 1PEA I node_15 HUMOSTROPEA 1_PEA_1node-17 HUMOSTROPEA1__PEA_1_node_20 WO 2005/072050 PCT/IB2005/000433 39 HLUMOSTROPEA_1_PEA_1_node_21 HUMOSTROPEA_1_PEAl-node_22 HUMOSTROPEA_1PEA_1_node_24 HUMOSTROPEA_1_PEA_1_node_26 HTUMOSTROPEA_1_PEA_1_node_27 HIUMOSTROPEA__PEA_1_node_28 HLUMOSTROPEA__PEA_1_node_29 HUMOSTROPEA_1_PEA_1_node_30 HUMOSTROPEA_1 PEA_1_node_32 HUMOSTROPEA_ IPEA-_node_34 HUMOSTROPEAI _PEA_1_node_36 HUMOSTROPEA1 _PEA_1_node_37 HUMOSTROPEA 1_PEA_1_node_38 HUMOSTROPEA_1_PEA_1_node_39 HUMOSTROPEA_1_PEA_1_node_40 HUMOSTROPEA-_1PEA _node_41 HUMOSTROPEA_ 1PEA_1_node_42 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HUMOSTROPEA_1_PEAlP21 HUMOSTROPEAlPEA__P25 HUMOSTROPEA_-PEA_1_P30 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a polynucleotide having a sequence selected from the group consisting of: RI 1723_PEA-1_TI5, RI 1723_PEA_1_T17, RI 1723-PEAI_T19, R11723-PEAlT20, R11723_PEA-lT5, or R11723_PEA-lT6.

WO 2005/072050 PCT/IB2005/000433 40 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a rode having a sequence selected from the group consisting of: R11723_PEAInode_ 13, RI 1723-PEA_1_node-16, R 1723_PEA_1_node_19, R11723_PEA1_lnode_2, R11723_PEA_1_node_22, RI 1723_PEA_1_node_31, 5 R11723_PEA_1_node 10, R11723_PEA_1_nodel 1, R11723PEA_1_node_15, R11723_PEA-1_node_18, R11723_PEA_1_node_20, R11723_PEA_1_node_21, R11723_PEA_1_node 23, R11723PEA_1_node_24, R11723_PEA__node_25, R11723-PEA 1_node 26, R11723_PEAInode_27, Ri 1723_PEA_1_node_28, R11723_PEA-1_node 29, R11723_PEA_1-node_3, R11723_PEA_1_node_30, 10 R11723_PEA_1-node_4, R11723_PEA_1_node_5, R11723_PEA_1node_6, Ri 1723_PEA_1_node_7 or RI 1723_PEA_1_node_8. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a polypeptide having a sequence selected from the group consisting of: R11723_PEA_1_P2, R11723_PEA_1-P6, R11723_PEA_1_P7, 15 R11723_PEA_1_P13, or R11723_PEA_1_PO. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name. T46984_PEAIT2 T46984_PEA_1_T3 T46984_PEA I_T12 T46984_PEA-_1T13 T46984_PEA_1-T14 T46984_PEA_1_Ti5 T46984_PEA1 _T19 T46984_PEA1 T23 T46984_PEA1 _T27 T46984_PEA_1_T32 T46984_PEA_1_T34 WO 2005/072050 PCT/IB2005/000433 41 T46984_PEA-_T35 T46984_PEA_1 T40 T46984-PEA_1_T42 T46984_PEA_1 T43 T46984-PEA_1_T46 T46984_PEA_1_T47 T46984_PEA_1_T48 T46984_PEAI _T51 T46984_PEA-lT52 T46984_PEA_1_T54 a nucleic acid sequence comprising a sequence in the table below: Segment Name T46984-PEA_1_node_2 T46984_PEA_1_node_4 T46984_PEA_1node_6 T46984_PEA 1 node-12 T46984-PEA__node_14 T46984_PEAInode_25 T46984_PEA_1_node_29 T46984_PEA_1_node_34 T46984_PEA_1_node_46 T46984_PEA_1_node_47 T46984_PEA_1 node_52 T46984_PEA_ l_node_65 T46984_PEA_1_node_69 T46984_PEA_1_node_75 T46984-PEA_1_node_86 WO 2005/072050 PCT/IB2005/000433 42 T46984 PEA 1node 9 T46984PEA-1_node_13 T46984_PEAInode 19 T46984_PEA-1_node_21 T46984_PEA_1_node_22 T46984_PEA_1_node_26 T46984_PEAInode_28 T46984_PEA._1node_31 T46984_PEA_1_node_32 T46984_PEA-1_node_38 T46984_PEA_1_node_39 T46984_PEAInode_40 T46984_PEAInode_42 T46984_PEA_1_node_43 T46984_PEA_1_node_48 T46984_PEA_1 node_49 T46984_PEA_1 node_50 T46984_PEA_1_node_51 T46984_PEA_1 node_53 T46984_PEA_1_node_54 T46984_PEA_1_node_55 T46984_PEAInode_57 T46984_PEA_1_node_60 T46984_PEA_1_node_62 T46984_PEA_1-node_66 T46984_PEA_1_node_67 T46984_PEA-_1node_70 T46984_PEA_1_node_71 T46984_PEA_1_node_72 T46984_PEA_1_node_73 WO 2005/072050 PCT/IB2005/000433 43 T46984-PEA-_node-74 T46984_PEAInode_83 T46984-PEA_1_node-84 T46984_PEA_1_node_85 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name T46984_PEA_1 P2 T46984_PEA_1 P3 T46984_PEA_1-PIO T46984_PEA_-P11 T46984_PEA_1 P12 T46984_PEA-1_P21 T46984_PEA_1 P27 T46984_PEA_1_P32 T46984_PEA_1_P34 T46984_PEA_1_P35 T46984_PEAlP38 T46984_PEA_1_P39 T46984_PEA_1_P45 T46984_PEA_1_P46 According to preferred embodiments of the present invention, there is provided an 5 isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name T11628_PEA_1 T3 TI1628_PEA-lT4 TI1628PEA_1_T5 WO 2005/072050 PCT/IB2005/000433 44 T11628PEA I T7 TI 1628PEA_1_T9 T11628_PEAI.Tll a nucleic acid sequence comprising a sequence in the table below: Segment Name T11628_PEA_1_node_7 TI1628_PEAI lnode 11 T11628_PEA 1_node 16 TI 1628_PEA_1_node_22 TI1628_PEAI1node_25 TI 1628_PEAI 1node_31 TI 1628_PEA_1_node_37 T11628_PEA_1_node_0 T11628_PEA 1 node_4 T 1628_PEAI node_9 T11628_PEA 1 node 13 T11628_PEA Inode 14 T11628_PEA _-node 17 T11628_PEA_1_node 18 TI 1628_PEA_1 node 19 TI 1628_PEA_1.node_24 T11628-PEA_ 1node 27 T11628_PEAInode_28 T 1628_PEA I node 29 T11628_PEA_1_node_30 T11628_PEA_1 node 32 TI 1628_PEA_1 node_33 WO 2005/072050 PCT/IB2005/000433 45 T11628_PEA_1_nxlAe_34 Tl1628-PEA_1_node_35 T11628_PEA_1_rode_36 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below 5 Protein Name T11628_PEA 1 P2 T1628_PEA_1 P5 TI 1628_PEA_1_P7 T11628_PEA_1 P10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name M78076_PEA_1_T2 M78076_PEA_1_T3 M78076_PEA_1_T5 M78076_PEA_1_T13 M78076_PEA_1_T15 M78076_PEA_1_T23 M78076_PEA-lT26 M78076_PEA_1-T27 M78076_PEAl-T28 a nucleic acid sequence comprising a sequence in the table below: Segment Name WO 2005/072050 PCT/IB2005/000433 46 M78076_PEA-_1node_0 M78076-PEA_1_node_10 M78076_PEA-1_node_15 M78076-PEA_1_node_18 M78076_PEA_1_node_20 M78076_PEA_1_node_24 M78076_PEA_1 node_26 M78076_PEA_1 node_29 M78076_PEAInode_32 M78076_PEA_1_node_35 M78076_PEA_1_node_37 M78076_PEA-_1node_46 M78076_PEA_1_node_47 M78076_PEA_1 node_54 M78076_PEA_1_node_1 M78076_PEA_1 node 2 M78076_PEA_1 node_3 M78076_PEA_1_node_6 M78076-PEA_1_node_7 M78076_PEA_1 node_12 M78076_PEA_1_node_22 M78076_PEA_1_node_27 M78076_PEA-_1node_30 M78076_PEA_1_node_31 M78076_PEA_1_node_34 M78076_PEA_1_node_36 M78076_PEA_1_node_41 M78076_PEA_1_node_42 M78076_PEA-_node_43 M78076_PEA_1_node_45 WO 2005/072050 PCT/IB2005/000433 47 M78076_PEA_1_node_49 M78076_PEA_1_node_50 M78076_PEA_1_node_51 M78076_PEA_1 node_52 M78076_PEA_1_node_53 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name M78076_PEA_1 P3 M78076_PEA_P4 M78076_PEA1 _P12 M78076_PEA_1_P14 M78076_PEA_1 P21 M78076_PEA_1_P24 M78076_PEA_1_P2 M78076_PEA_1-P25 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HSMUC1A_PEA_1-T12 HSMUC1A_PEA_1_T26 HSMUC1A_PEA_1_T28 HSMUC1APEA1 1T29 HSMUC1A_PEA_1-T30 HSMUCIAPEA1 _T31 HSMIUCIA_PEA_1_T33 HSMUC1APEA1 _T34 WO 2005/072050 PCT/IB2005/000433 48 HSMUC1APEA_1_T35 HSMUC1A_PEA_1-T36 HSMUC1APEAIT40 HSMLCIAPEAlT42 HSMUC1APEAlT43 HSMUC1APEAIT47 a nucleic acid sequence comprising a sequence in the table below: SegmentName HSMUC1APEA_1-node_0 HSMUC1A_PEA_1_node_14 HSMUClA_PEA_1_node_24 HSMUC1A-PEA__node_29 HSMUC1A_PEA_1_node_35 HSMUC1APEA_1_node_38 HSMUC1A_PEA-_1node_3 HSMUJC1A_PEA-lInode_4 HSMUCIA_PEA_1_node_5 HSMUCIAPEA_1_node_6 HSMUC1A_PEAInode_7 HSMUC1A_PEA_1_node_17 HSMUC1A_PEA-1_node_18 HSMUC1APEA_1_node_20 HSMUC1A_PEA_.Inode_21 HSMUC1A-PEA_1_node_23 HSMUC1A_PEA_1_node_26 HSMUC1A-PEA_1_node_27 HSMUC1A_PEA_1_node_31 WO 2005/072050 PCT/IB2005/000433 49 HSMUCIAPEA_1_node_34 HSMUCIA_PEA_1_node_36 HSMUC1APEA_1 node 37 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HSMUC1APEA 1 P25 HSMUC1APEA 1 P29 HSMUC1A PEA 1_P30 HSMUC1APEA 1 P32 HSMUCIAPEA 1 P36 HSMULJC1APEA 1 P39 HSMUC1A PEA 1 P45 HSMUC1A PEA 1_P49 HSMUCIAPEA_lP52 HSMLC1APEA 1_P53 HSMUC1APEA 1 P56 HSMUC1A_PEAl-P58 HSMUC1APEA_1 P59 HSMUC1APEA_1_P63 5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSMUIJC1A_PEA_1 P63, comprising a first amino acid sequence being at least 90 % homologous to MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1 - 45 of MUC_-HUMAN, which also corresponds to amino acids 1 - 45 of 10 HSMUC1A_PEA_1_P63, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072050 PCT/IB2005/000433 50 EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK corresponding to amino acids 46 - 85 of HSMIJC1A_PEA_1_P63, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of HSMUC1A_PEA_1_P63, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK in HSMUCIAPEA_1_P63. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for T46984_PEALP2, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI 15 VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS 20 ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1 - 498 of RIB2_HUMAN, which also corresponds to amino acids 1 - 498 of T46984_PEA-l_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VCA corresponding to amino acids 499 - 501 of T46984_PEA-1_P2, wherein said first amino 25 acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEAlP3, comprising a first amino acid sequence being at least 90 % homologous to 30 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL

GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS

WO 2005/072050 PCT/IB2005/000433 51 VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN 5 RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQ corresponding to amino acids 1 - 433 of RIB2_HUMAN, which also corresponds to amino acids 1 - 433 of T46984_PEA_1_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 ICHIWKLIFLP corresponding to amino acids 434 - 444 of T46984-PEA_1_P3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA-lP3, comprising a polypeptide being 15 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ICHIWKLIFLP in T46984_PEA_1_P3. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984-PEA-1_P10, comprising a first amino acid 20 sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA 25 IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAJILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNV'KFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1 - 498 of RIB2_HUIAN, 30 which also corresponds to amino acids 1 - 498 of T46984_PEA_1_PlO, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more WO 2005/072050 PCT/IB2005/000433 52 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LMIDQK corresponding to amino acids 499 - 503 of T46984_PEA_1_P10, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEAI_PO, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LMDQK in T46984-PEA_1_PO. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA_1._P11, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS 15 VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL 20 FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEK RPPTVVSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWT QLNMFQTLKYLAILGSVTFLAGNRMLAQQAVEKR corresponding to amino acids I - 628 of RIB2_HUMAN, which also corresponds to amino acids 1 - 628 of T46984_PEA_1_P11. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEAI_P12, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL 30 GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS

VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHISQQADLRSI

WO 2005/072050 PCT/IB2005/000433 53 VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHIVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPiVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMN corresponding to amino acids 1 - 338 of RIiB2_HUMAN, which also corresponds to amino acids I - 338 of 5 T46984_PEA_1_P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SQDLH corresponding to amino acids 339 343 of T46984_PEA_1_P12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SQDLH in T46984_PEA_1_P12. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA_1_P21, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence M corresponding to amino acids 1 - 1 of T46984_PEA-1_P21, and a second amino acid sequence 20 being at least 90 % homologous to KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSSVTQIYHAV AALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVA RLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFES LSEAFSVASAAAVLSHNRYHVPVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKL 25 EHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVEL RVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQLVDVNT GAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDSASGTYTLYLII GDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLF REPEKRPPTVVSNTF TALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKY 30 LAILGSVTFLAGNRMLAQQAVKRTAH corresponding to amino acids 70 - 631 of RIB2_HUMAN, which also corresponds to amino acids 2 - 563 of T46984_PEA_1_P21, WO 2005/072050 PCT/IB2005/000433 54 wherein said first amino acid seqance and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA_lP27, comprising a first amino acid 5 'sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHISQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA 10 IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVTKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFA corresponding to amino acids I - 415 of RIB2_HUMAN, which also corresponds to amino acids 1 - 415 of T46984_PEA_1_P27, and a second amino acid sequence being at least 70%, 15 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP corresponding to amino acids 416 - 459 of T46984_PEA_._P27, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984-PEA_1_P27, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP in 25 T46984 PEA 1 P27. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984-PEA_1_P32, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL 30 GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS

VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASLSQQADLRSI

WO 2005/072050 PCT/IB2005/000433 55 VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVE corresponding to amino acids 1 - 364 of RIB2_HUMAN, which also corresponds 5 to amino acids 1 - 364 of T46984_PEA_lP32, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT corresponding to amino acids 365 - 397 of T46984_PEA-lP32, wherein said first amino acid sequence and second amino acid 10 sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA_1_P32, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 15 GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT in T46984_PEA-lP32. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA_lP34, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL 20 GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVG corresponding to amino acids I - 329 of 25 RIB2-HUMAN, which also corresponds to amino acids 1 - 329 of T46984-PEA_1_P34. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA-lP35, comprising a first amino acid sequence being at least 90 % homologous to 30 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL

GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS

WO 2005/072050 PCT/IB2005/000433 56 VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI corresponding to amino acids I - 287 of RIB2_HUMAN, which also corresponds to amino acids 1 - 287 of 5 T46984_PEA_1_P35, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTHSMRRKM[EKKNFI corresponding to amino acids 288 - 334 of T46984_PEA-lP35, wherein said first amino acid sequence and 10 second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA_1_P35, comprising a polypeptide being at least 70%, optiomlly at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 15 GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI in T46984_PEA_1_P35. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEALP38, comprising a first amino acid sequence being at least 90 % homologous to 20 MAPPGSSTVFLLALTIIASTWALTPTHY[LTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEAL corresponding to amino acids 1 - 145 of RI32_HUMAN, which also corresponds to amino acids I - 145 of T46984_PEAlP38, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 25 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDPDWCQCLQLHFCS corresponding to amino acids 146 - 160 of T46984_PEA_1_P38, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of T46984_PEA_1_P38, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072050 PCT/IB2005/000433 57 least about 90% and most preferably at least about 95% homologous to the sequence MDPDWCQCLQLHFCS in T46984_PEA_1_P38. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for T46984_PEA_1_P39, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLA corresponding to amino acids 1 10 160 of RI!B2_HUMAN, which also corresponds to amino acids 1 - 160 of T46984_PEA_1_P39. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA-lP45, comprising a first amino acid sequence being at least 90 % homologous to 15 MAPPGSSTVFLLALTJIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCE corresponding to amino acids 1 - 101 of RIB2_-HUMAN, which also corresponds to amino acids 1 - 101 of T46984_PEA_1_P45, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 20 homologous to a polypeptide having the sequence NSPGSADSIPPVPAG corresponding to amino acids 102 - 116 of T46984_PEAlP45, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEAlP45, comprising a polypeptide being 25 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG in T46984_PEAlP45. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA-lP46, comprising a first amino acid 30 sequence being at least 90 % homologous to

MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL

WO 2005/072050 PCT/IB2005/000433 58 GAQVPDAK corresponding to amino acids 1 - 69 of RIiB2-HUMAN, which also corresponds to amino acids 1 - 69 of T46984-PEA-lP46, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 NSPGSADSIPPVPAG corresponding to amino acids 70 - 84 of T46984_PEA_1_P46, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA-lP46, comprising a polypeptide being 10 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG in T46984_PEA_1_P46. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T 11628PEA_1_P2, comprising a first amino acid 15 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE corresponding to amino acids 1 - 55 of TI 1628_PEA_1_P2, and a second amino acid sequence being at least 90 % homologous to 20 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHIIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1 - 99 of Q8WVH6, which also corresponds to amino acids 56 - 154 of T I1628_PEA-_P2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of TI 1628_PEALP2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE of 30 T11628_PEA 1 P2.

WO 2005/072050 PCT/IB2005/000433 59 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Ti 1628_PEA_1_P5, comprising a first amino acid sequence being at least 90 % homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV 5 LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56 - 154 of MYG_HUMAN_VI, which also corresponds to amino acids 1 - 99 of T11628-PEAI_P5. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for T11628_PEAlP7, comprising a first amino acid sequence being at least 90 % homologous to MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMK ASEDLKKHGATVLTALGGILKKKGIIEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQ SKHPGDFGADAQGAMNK corresponding to amino acids I - 134 of MYG_HUMAN_V1, 15 which also corresponds to amino acids 1 - 134 of T11628_PEAl-P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence G corresponding to amino acids 135 - 135 of T11628_PEA-1_P7, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA_1_PO, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE 25 corresponding to amino acids 1 - 55 of T11628-PEA_1_PlO, and a second amino acid sequence being at least 90 % homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1 - 99 of Q8WVH6, which also corresponds to amino acids 56 - 154 of 30 T11628_PEA_1_PlO, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 60 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of TI 1628_PEA_1_Pl0, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE of T11628-PEA_1_P1O. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA-_LP3, comprising a first amino acid sequence being at least 90 % homologous to 10 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLIHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV 15 DIYFGMPGEISEHEGFLRAKMDLEERRMRQINETvREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids I - 517 of APPiHUMAN, which also corresponds to amino acids I - 517 of 20 M78076_PEA_1 P3, and a second amino acid sequence being at least 70%, optionally at least 8 0

%

, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GE corresponding to amino acids 518 - 519 of M78076_PEA-lP3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA-_LP4, comprising a first amino acid sequence being at least 90 % homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME 30 RWCGGSRSGSCA HPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ

EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG

WO 2005/072050 PCT/IB2005/000433 61 SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD 5 QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1 - 526 of APPi-HUMAN, which also corresponds to amino acids 1 - 526 of M78076_PEA_1_P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 ECLTVNPSLQIPLNP corresponding to amino acids 527 - 541 of M78076_PEA_1_P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA-lP4, comprising a polypeptide being 15 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECLTVNPSLQIPLNP in M78076_PEA-lP4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076-PEA_1_P12, comprising a first amino acid 20 sequence being at least 90 % homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG 25 SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVIREWAADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG 30 corresponding to amino acids 1 - 526 of APPIHTUIAN, which also corresponds to amino acids 1 - 526 of M78076-PEA_1_P12, and a second amino acid sequence being at least 70%, WO 2005/072050 PCT/IB2005/000433 6 2 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECVCSKGFPFPLIGDSEG corresponding to amino acids 527 - 544 of M78076-PEA_1_P12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 5 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 ECVCSKGFPFPLIGDSEG in M78076_PEA_1_P12. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA_1 P14, comprising a first amino acid sequence being at least 90 % homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL 15 CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN 20 EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVJIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGST EQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDEL corresponding to amino acids I - 570 of APP IHUIMAN, which also corresponds to amino acids 1 - 570 of 25 M78076_PEA-l_P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP corresponding to amino acids 571 - 619 of M78076_PEA_1_P14, wherein said first amino acid sequence and 30 second amino acid sequence are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 63 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA1 P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP in M78076_PEA_-P14. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA-lP21, comprising a first amino acid sequence being at least 90 % homologous to 10 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV 15 DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN E corresponding to amino acids I - 352 of APPl_HUMAN, which also corresponds to amino acids 1 - 352 of M78076-PEA_1_P21, and a second amino acid sequence being at least 90 % homologous to AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQ 20 SLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMT LPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREA VSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYE NPTYRFLEERP corresponding to amino acids 406 - 650 of APP 1_HUMAN, which also corresponds to amino acids 353 - 597 of M78076_PEA_1_P21, wherein said first amino acid 25 sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of M78076_PEA_1_P21, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 30 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EA, having a WO 2005/072050 PCT/IB2005/000433 64 structure as follows: a sequence starting from any of amino acid numbers 352-x to 352; awJ ending at any of amino acid numbers 353+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for M78076-PEAlP24, comprising a first amino acid sequence being at least 90 % homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ 10 EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGNPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD 15 QNPHLAQELRPQI corresponding to amino acids I - 481 of APP I-HUMAN, which also corresponds to amino acids I - 481 of M78076_PEA_1_P24, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RECLLPWLPLQISEGRS corresponding to amino acids 482 - 498 of M78076_PEA-lP24, 20 wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEAlP24, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 25 at least about 90% and most preferably at least about 95% homologous to the sequence RECLLPWLPLQISEGRS in M78076_PEA_1_P24. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEAlP2, comprising a first amino acid sequence being at least 90 % homologous to 30 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL

CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME

WO 2005/072050 PCT/IB2005/000433 65 RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN 5 EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQR[HTLRHYQHVAAVDPEKAQQMIRFQV corresponding to amino acids I - 449 of APPI_HUMAN, which also corresponds to amino acids 1 - 449 of M78076_PEAlP2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 10 homologous to a polypeptide having the sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE corresponding to amino acids 450 - 588 of M78076-PEA-lP2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 15 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA-lP2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE in M78076_PEA_1_P2. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for M78076_PEA_1_P25, comprising a first amino acid sequence being at least 90 % homologous to MGPASPAARGLSRRPGQPPLP LLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVTLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERvIDQCESSTRRHQ 30 EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG

SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV

WO 2005/072050 PCT/IB2005/000433 66 DIYFGM/PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQIHVAAVDPEKAQQMRFQ corresponding to amino acids I - 448 of APPi_HUMAN, which also corresponds to amino acids 1 - 448 of 5 M78076_PEA_1_P25, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP corresponding to amino acids 449 - 505 of M78076_PEA_lP25, wherein said first amino acid 10 sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA_1_P25, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 15 PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP in M78076_PEA_1_P25. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M85491_PEA-_1P13, comprising a first amino acid sequence being at least 90 % homologous to 20 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN 25 SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL QYYEK corresponding to amino acids 1 - 476 of EPB2_HUMAN, which also corresponds to amino acids 1 - 476 of M85491_PEA_1_P13, and a second amino acid sequence being at least 30 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072050 PCT/IB2005/000433 67 VPIGWVLSPSPTSLRAPLPG corresponding to amino acids 477 - 496 of M85491_PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of M85491_PEA_1_P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG in M85491_PEA_1_P13. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for M85491_PEA_1_P14, comprising a first amino acid sequence being at least 90 % homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF 15 YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1 270 of EPB2_HUMAN, which also corresponds to amino acids I - 270 of M85491-PEA_1_P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 20 homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVTLEL corresponding to amino acids 271 - 301 of M85491-PEA_1_P14, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a tail of M85491-PEA_1 P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL in M85491_PEA_1_P14. 30 According to prefered embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P4, comprising a first amino acid WO 2005/072050 PCT/IB2005/000433 68 sequence being at least 90 % homologous to MAPAAVWL.RSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to 5 amino acids 1 - 163 of MM 1_I-HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3_P4, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4, a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPVPTVTSRTPALGPQAGIDTN 10 EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHA-ALVWGPE KNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG corresponding to amino acids 165 - 445 of MM1 I_-HUMAN, which also corresponds to amino acids 165 - 445 of HSSTROL3_P4, and a third amino acid sequence being at least 70%, optionally at least 80%, 15 preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG corresponding to amino acids 446 - 496 of HSSTROL3_P4, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are 20 contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG in HSSTROL3_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P5, comprising a first amino acid 30 sequence being at least 90 % homologous to

MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS

WO 2005/072050 PCT/IB2005/000433 69 PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1 - 163 of MM I 1_HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3_P5, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5, 5 a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALM\SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165 - 358 of MMl I HUMAN, 10 which also corresponds to amino acids 165 - 358 of HSSTROL3_P5, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK corresponding to amino acids 359 - 382 of HSSTROL3_P5, wherein said first amino acid sequence, bridging amino acid, second amino 15 acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3 P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 ELGFPSSTGRDESLEHCRCQGLHK in HSSTROL3_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P7, comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS 25 PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids I - 163 of MMl 1_HUMAN, which also corresponds to amino acids I - 163 of HSSTROL3_P7, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7, a second amino acid sequence being at least 90 % homologous to 30 GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG

LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN

WO 2005/072050 PCT/IB2005/000433 70 EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165 - 359 of MMl I_HUMAN, which also corresponds to amino acids 165 - 359 of HSSTROL3 P7, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 5 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV corresponding to amino acids 360 - 370 of HSSTROL3 P7, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of HSSTROL3_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P7. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for HSSTROL3_P8, comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAA ARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTY LRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to 20 amino acids I - 163 of MM I HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3_P8, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3-PS, a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHIEFGH-VLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN 25 EAPLE corresponding to amino acids 165 - 286 of MMl I_HJUIAN, which also corresponds to amino acids 165 - 286 of HSSTROL3-P8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL corresponding to amino acids 287 - 301 of HSSTROL3_P8, wherein 30 said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 71 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3-PS, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 VRPCLPVPLLLCWPL in HSSTROL3_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P9, comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHYLHAERRGPQPWHAALPSS 10 PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids I 96 of MMl 1_HUMAN, which also corresponds to amino acids I - 96 of HSSTROL3-P9, a second amino acid sequence being at least 90 % homologous to RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113 - 163 of MMi l-HUMAN, which also corresponds to amino 15 acids 97 - 147 of HSSTROL3_P9, a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9, a third amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRITWQGL 20 PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165 - 359 of MM I_-HUMAN, which also corresponds to amino acids 149 - 343 of HSSTROL3-P9, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV corresponding to amino acids 344 - 354 of HSSTROL3 P9, wherein said first 25 amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 30 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino WO 2005/072050 PCT/IB2005/000433 72 acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96; and ending at any of amino acid numbers 97+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of HSSTROL3_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P9. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for AYI 80924_PEA_ P3, comprising a first amino acid sequence being at least 90 % homologous to MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN corresponding to amino acids 1 - 33 of LATHHUMAN, which also corresponds to amino acids 1 - 33 of AYI80924_PEA_1 P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 15 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GETVLLWYMQNPEPMPVKFSLAKYLGHNEHY corresponding to amino acids 34 - 64 of AY 180924 PEA-_ P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of AYl 80924_PEAl-P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GETVLLWVMQNPEPMPVKFSLAKYLGItNEHY in AY180924_PEAlP3. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R75793-PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAATTATTAAPT TATTAASTTARKDIP corresponding to amino acids 1 - 74 of Q96DR8, which also 30 corresponds to amino acids 1 - 74 of R75793_PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least WO 2005/072050 PCT/IB2005/000433 73 90% and most preferably at least 95% homologous to a polypeptide having the sequence AP corresponding to amino acids 75 - 76 of R75793_PEA-lP2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HLUMCA LXIA_P14, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY 10 NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVCEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN 15 GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG 20 PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGTGPRGVK GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG 25 LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1 - 1056 of CAIB-HUMANV5, which also corresponds to amino acids 1 - 1056 of HUMCAlXIA.P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 VSMMIINSQTIMVVNYSSSFITLML corresponding to amino acids 1057 - 1081 of WO 2005/072050 PCT/IB2005/000433 74 HUMCA1XIAP14, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HJMCA IXIAP14, comprising a polypeptide being 5 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSMMIINSQTIMVVNYSSSFITLML in HUMCAIXIAP14. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCAIXIA_P15, comprising a first amino acid 10 sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH 15 YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMILPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM 20 GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1 - 714 of CAIBHUMIAN, which also corresponds to amino acids 1 - 714 of HUMCA IXIAP15, and a second amino acid sequence being at least 25 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK corresponding to amino acids 715 - 729 of HUMCAIXIAP15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCAlXIAP15, comprising a polypeptide being WO 2005/072050 PCT/IB2005/000433 75 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK in HUMCAIXIAP15. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for HUMCA IXIA_P16, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM 10 IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAP RHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG 15 RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMI.P GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1 - 648 of CAI B-HIUMAN, which also corresponds to amino acids 1 - 648 of HUTMCA I XIAP16, a second amino acid sequence being at least 90 % 20 homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667 - 714 of CA 1 B_HUMAN, which also corresponds to amino acids 649 - 696 of HUMCAIXIA_P16, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE corresponding to amino acids 697 - 738 of HUMCAIXIAP16, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HIUMCAIXIAP16, comprising a 30 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more WO 2005/072050 PCT/IB2005/000433 76 preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+ ((n-2) - x), in which x varies from 0 to n-2. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HlUMCA IXIA_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE in HUMCA1XIA P16. 10 According to preferred embodiments of the present invertion, there is provided an isolated chimeric polypeptide encoding for HUMCA 1 XIA_P17, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY 15 NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids I - 260 of CAIB_HUMAN, which also corresponds to amino acids I - 260 of HUMCAlXIA_P17, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 20 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ corresponding to amino acids 261 - 273 of HUMCA I XIA_P17, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a tail of HUMCAIXIA_P17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ in HUMCAIXIA_P17. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for R20779_P2, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 77 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLV NAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRH RFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1 - 169 of STC2_HUMAN, which also corresponds to amino 5 acids 1 - 169 of R20779_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 9 0% and most preferably at least 95% homologous to a polypeptide having the sequence CYKIEITMPKRRKVKLRD corresponding to amino acids 170 - 187 of R20779_P2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R20779P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD in R20779_P2. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA1 _P3, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 20 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGV AYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHI1SLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRILVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 25 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAA-PPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 30 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID

EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL

WO 2005/072050 PCT/IB2005/000433 78 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTV corresponding to amino acids 1 865 of C04_HUMAN, which also corresponds to amino acids 1 - 865 of HSCOC4_PEA_1-P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 9 0% and most preferably at least 95% homologous to a 5 polypeptide having the sequence RPiRSLSIQELGEPGPSEGWGG corresponding to amino acids 866 - 887 of HSCOC4_PEA_1_P3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEAlP3, comprising a polypeptide 10 being at least 70%, optionally at least about 80 %, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RPHRSLSIQELGEPGPSEGWGG in HSCOC4_PEA_1_P3. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEAI_P5, comprising a first amino acid 15 sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 20 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVS\TFVDHIHLA 25 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIIHGLSLSKTKG corresponding 30 to amino acids 1 - 818 of C04_HUMAN, which also corresponds to amino acids I - 818 of HSCOC4_PEA_--P5, and a second amino acid sequence being at least 70%, optionally at least WO 2005/072050 PCT/IB2005/000433 79 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS corresponding to amino acids 819 - 843 of HSCOC4_PEA_1_P5, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4-PEA-lP5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS in HSCOC4_PEA_1-P5. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLK-DAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGLLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 25 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALELLQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL 30 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKG corresponding to amino acids 1 - 1052 of C04_HUMAN, which also corresponds to amino acids 1 - 1052 of WO 2005/072050 PCT/IB2005/000433 80 HSCOC4-PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP corresponding to amino acids 1053 5 1084 of HSCOC4_PEA_1_P6, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA-lP6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 10 at least about 90% and most preferably at least about 95% homologous to the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP in HSCOC4_PEA_1_P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P12, comprising a first amino acid sequence being at least 90 % homologous to 15 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR 20 GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS 25 LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 30 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL

VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL

WO 2005/072050 PCT/IB2005/000433 81 LRLPRGCGEQTIIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 5 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKV corresponding to amino acids 1 - 1380 of C04_HUMAN_VI, which also corresponds to amino acids 1 - 1380 of HSCOC4_PEA_1_P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 10 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RAREGVGPGTGGGEGVE corresponding to amino acids 1381 - 1397 of HSCOC4PEAP12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RAREGVGPGTGGGEGVE in HSCOC4_PEA_1_P12. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for HSCOC4_PEA_1_'P15, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV 25 ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD 30 SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA

PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS

WO 2005/072050 PCT/IB2005/000433 82 LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 5 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ 10 DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGA-IAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQ corresponding to amino acids I - 1359 of C04_HUMANV1, which also 15 corresponds to amino acids 1 - 1359 of HSCOC4_PEA_1_P15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL corresponding to amino acids 1360 - 1415 of HSCOC4_PEA_1_P15, wherein said first amino 20 acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA-_P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL in HSCOC4_PEA_1_P15. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P16, comprising a first amino acid sequence being at least 90 % homologous to 30 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR

NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK

WO 2005/072050 PCT/IB2005/000433 83 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPYNIPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 5 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIUPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHWVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 10 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLW LPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 15 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 20 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKJNVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPK corresponding to amino acids 1 - 1457 of C04-HUMAN V1, which also corresponds to amino acids I - 1457 25 of HSCOC4_PEA_1-P16, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AERQGGAVWHGHRGRHPPEWIPRPAC corresponding to amino acids 1458 - 1483 of HSCOC4_PEA_1_P16, wherein said first amino acid sequence and second amino acid sequence 30 are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 84 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_1 P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 AERQGGAVWHGHRGRHPPEWIPRPAC in HSCOC4_PEA_1_P16. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEAlP20, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR 10 NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDI.QARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 15 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHIIHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEA4NSYDLGCGPGGGDSALQVFQAAG 20 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVlDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFILHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 25 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 30 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQ corresponding to amino acids I - 1303 of C04_HUMAN_VI, which also WO 2005/072050 PCT/IB2005/000433 85 corresponds to amino acids 1 - 1303 of HSCOC4_PEA_1_P20, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH corresponding to 5 amino acids 1304 - 1349 of HSCOC4_PEA_1_P20, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA-lP20, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 10 at least about 90% and most preferably at least about 95% homologous to the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH in HSCOC4_PEA_1_P20. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA-lP9, comprising a first amino acid 15 sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 20 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMLLSRGQIVFMNREPKRTLTSVSVFVDHHLA 25 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 30 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ

QVLV\PAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL

WO 2005/072050 PCT/IB2005/000433 86 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMvRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS 5 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV 10 HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1 - 1529 of C04-HIJMAN_VI, which also corresponds to amino acids 1 - 1529 of HSCOC4_PEA_1_P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER 15 corresponding to amino acids 1530 - 1533 of HSCOC4_PEA_1_P9, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 20 at least about 90% and most preferably at least about 95% homologous to the sequence SGER in HSCOC4_PEA_1_P9. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4-PEA-lP22, comprising a first amino acid sequence being at least 90 % homologous to 25 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMiWSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR 30 GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE

LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP

WO 2005/072050 PCT/IB2005/000433 87 EVQDIQQNTDGSGQVSIUPIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKILHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 5 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALELQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 10 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAIIAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 15 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL 20 YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAF RLFETKITQVLHF corresponding to amino acids 1 - 1653 of C04_HUMAN_VI, which also corresponds to amino acids 1 - 1653 of HSCOC4_PEA_1_P22, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 25 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SMKQTGEAGRAGGRQGG corresponding to amino acids 1654 - 1670 of HSCOC4_PEA-1_P22, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably WO 2005/072050 PCT/IB2005/000433 88 at least about 90% and most preferably at least about 95% homologous to the sequence SMKQTGEAGRAGGRQGG in HSCOC4_PEA_1_P22. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1-P23, comprising a first amino 5 acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 10 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA 15 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 20 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQEKEGA-IHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ 25 DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLIHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE 30 YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV

HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL

WO 2005/072050 PCT/IB2005/000433 89 YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYG corresponding to amino acids I - 1626 of C04_HUMAN_VI, which also corresponds to amino acids 1 - 1626 of HSCOC4_PEA-lP23, and a second amino acid sequence being at least 70%, optionally at 5 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS corresponding to amino acids 1627 - 1685 of HSCOC4_PEA_1_P23, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA-1_P23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS in 15 HSCOC4_PEA_1_P23. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P24, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR 20 NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEIEEAE 25 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKL-LETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 30 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR

LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID

WO 2005/072050 PCT/IB2005/000433 90 EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATP VQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL 5 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR 10 QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMIEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDS corresponding to amino acids 1 - 1528 of C04_-HUMAN_Vi, which also corresponds to 15 amino acids 1 - 1528 of HSCOC4_PEA_1_P24, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG corresponding to amino acids 1529 - 1579 of HSCOC4_PEAI_P24, wherein said first amino 20 acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P24, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG in HSCOC4_PEA_1_P24. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEAlP25, comprising a first amino acid sequence being at least 90 % homologous to 30 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR

NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK

WO 2005/072050 PCT/IB2005/000433 91 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 5 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIA-RLTVAAPPSGGPGFLSI]ERPD SRPPRVGDTLNLNLRAVGSGATFSHYYiYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 10 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIREEL 15 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAM1AQETGDNLYWGSV 20 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL 25 YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids I - 1593 of C04_HUMAN-V, which also corresponds to amino acids 1 - 1593 of HSCOC4-PEA_1_P25, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 8 5%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG corresponding to amino acids 1594 - 1657 of HSCOC4_PEA_1_P25, wherein said WO 2005/072050 PCT/IB2005/000433 92 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEAl_P25, comprising a polypeptide 5 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG in HSCOC4_PEA_1_P25. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for HSCOC4_PEA_lP26, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQ LQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV 15 ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD 20 SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKL HLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID 25 EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK 30 ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIAL HHGLAVFQDEGAEPLKQRVEASISKASS WO 2005/072050 PCT/IB2005/000433 93 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE 5 YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1 - 1593 of C04_HUMAN_Vi, which also corresponds to amino acids I - 1593 of HSCOC4_PEA_1_P26, and a second amino acid 10 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL corresponding to amino acids 1594 - 1691 of HSCOC4_PEA_1_P26, wherein said first amino acid sequence and second 15 amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEAl-P26, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL in HSCOC4_PEAlP26. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4-PEA_1_P30, comprising a first amino acid sequence being at least 90 % homologous to 25 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR 30 GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE

LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP

WO 2005/072050 PCT/IB2005/000433 94 EVQDIQQNT)GSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 5 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQLTLWLPDSLTTWEIHGLSLSKTKGLCVJATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 10 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMIPJQQFRK ADGSYAAWLSRDSSTVLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 15 corresponding to amino acids 1 - 1232 of C04-HUMAN-V3, which also corresponds to amino acids 1 - 1232 of HSCOC4_PEA_1_P30, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RNPVRLLQPRAQMFCVLRGTK corresponding to amino acids 1233 - 1253 of 20 HSCOC4_PEA_1_P30, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P30, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 25 at least about 90% and most preferably at least about 95% homologous to the sequence RNPVRLLQPRAQMFCVLRGTK in HSCOC4_PEA_1_P30. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA._1P38, comprising a first amino acid sequence being at least 90 % homologous to 30 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR

NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK

WO 2005/072050 PCT/IB2005/000433 95 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYIMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 5 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNIREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLIHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 10 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids I - 818 of C04_H{UMAN, which also corresponds to amino acids 1 - 818 of HSCOC4_PEA_1 P38, and a second amino acid sequence being at least 70%, optionally at 15 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS corresponding to amino acids 819 - 843 of HSCOC4_PEA_1 P38, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of HSCOC4-PEA_1-P38, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS in HSCOC4_PEA_1_P38. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for HSCOC4-PEAlP39, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVV[KGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV 30 ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL

PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR

WO 2005/072050 PCT/IB2005/000433 96 GLESQTKLVNGQSIIISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ corresponding to amino acids 1 - 387 of CO4_HUMAN, which also corresponds to amino acids 1 - 387 of HSCOC4_PEA-lP39, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 5 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSSRGEG corresponding to amino acids 388 - 394 of HSCOC4_PEAlP39, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of HSCOC4_PEA-lP39, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSSRGEG in HSCOC4_PEA_1_P39. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P40, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVV&KGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV 20 ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY corresponding to amino acids 1 - 236 of C04_HUMAN, which also corresponds to amino acids 1 - 236 of HSCOC4_PEA1 _P40, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 AGEWTEPHIFPLKGRVPGRPGEAEYGHY corresponding to amino acids 237 - 263 of HSCOC4_PEA_-lP40, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_lP40, comprising a polypeptide 30 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably WO 2005/072050 PCT/IB2005/000433 97 at least about 90% and cost preferably at least about 95% homologous to the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY in HSCOC4 PEA_1_P40. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA-lP41, comprising a first amino 5 acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGNLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 10 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALV7REMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYILSRGQIVFNREPKRTLTSVSVFVDHHLA 15 PSFYFTVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQY-RNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFTQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMM4RSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 20 RVFREFHLHLRLPMSVRR-FEQLELRPVLYNYLDKNLTVSV7HVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMI4PDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGY MRIQQFRK ADGSYAAWLSRDSSTWLTAFVrLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ 25 DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTK-APADLRGVAHNNLM4AMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIfETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYxNVLDMKNTTCQDLQIEVTVKGHVIE 30 YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVV\EEQESRV

H[YTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL

WO 2005/072050 PCT/IB2005/000433 98 YFDSV corresponding to amino acids 1 - 1529 of CO4ILTMAN_VI, which also corresponds to amino acids 1 - 1529 of HSCOC4_PEA_1_P41, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER 5 corresponding to amino acids 1530 - 1533 of HSCOC4_PEAlP41, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P41, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 10 at least about 90% and most preferably at least about 95% homologous to the sequence SGER in HSCOC4-PEA_1-P41. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P42, comprising a first amino acid sequence being at least 90 % homologous to 15 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR 20 GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS 25 LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 30 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL

VTYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL

WO 2005/072050 PCT/IB2005/000433 99 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 5 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMIEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIW corresponding to amino acids 1 - 1473 of C04_HUMANV1, which also 10 corresponds to amino acids 1 - 1473 of HSCOC4-PEA_1_P42, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR corresponding to amino acids 1474 - 1511 of HSCOC4_PEA_1_P42, a third amino acid sequence being at least 90 % 15 homologous to RNGKVGLSGMALADVTLLSGFHALRADLEK corresponding to amino acids 1474 - 1503 of C04_HUMANV1, which also corresponds to amino acids 1512 - 1541 of HSCOC4_PEA-_lP42, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWSATQGNPLCPRY corresponding to 20 amino acids 1542 - 1555 of HSCOC4_PEA_1_P42, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of HSCOC4_PEAlP42, comprising an 25 amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR, corresponding to HSCOC4_PEA_1-P42. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of HSCOC4-PEA_LP42, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably WO 2005/072050 PCT/IB2005/000433 100 at least about 90% and most preferably at least about 95% homologous to the sequence VWSATQGNPLCPRY in HSCOC4_PEA_1_P42. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMTREFACPEA_2_P8, comprising a first 5 amino acid sequence being at least 90 % homologous to MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1 - 27 of TFF3_HULAN, which also corresponds to amino acids 1 - 27 of HUMTREFACPEA_2_P8, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 10 polypeptide having the sequence WKVHLPKGEGFSSG corresponding to amino acids 28 - 41 of HUMTREFACPEA_2_P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUTTREFAC-PEA_2-P8, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG in HUMTREFACPEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HIJMOSTROPEA_1_PEA_1_P21, comprising a 20 first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ corresponding to amino acids I - 58 of OSTPHUMAN, which also corresponds to amino acids I - 58 of HUMOSTROPEA_1_PEA_1_P21, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 25 preferably at least 95% homologous to a polypeptide having the sequence VFLNFS corresponding to amino acids 59 - 64 of HUMOSTROPEAIPEA_1_P21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTRO-PEA-_PEA_1_P21, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 101 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VFLNFS in HUMOSTROPEA_1-PEA-lP21. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HLTMOSTROPEA_1_PEA_1-P25, comprising a 5 first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids I - 31 of OSTPHUMAN, which also corresponds to amino acids 1 - 31 of HUMOSTROPEA_1_PEALP25, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 10 preferably at least 95% homologous to a polypeptide having the sequence H corresponding to amino acids 32 - 32 of HUMOSTROPEA_1_PEA-1-P25, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTROPEA_1_PEA-lP30, comprising a 15 first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids I - 31 of OSTP_HUMAN, which also corresponds to amino acids 1 - 31 of HUMOSTROPEA-1_PEAl-P30, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence VSIFYVFI corresponding to amino acids 32 - 39 of HUIMOSTROPEA_1_PEA_1- P30, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTROPEA_1_PEA_1_P30, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSIFYVFI in HUMOSTROPEA_1_PEA_1_P30. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA_1_P2, comprising a first amino acid WO 2005/072050 PCT/IB2005/000433 102 sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL 5 WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1 - 319 of CEA6_HUMAN, which also corresponds to amino acids 1 - 319 of T10888_PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 10 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP corresponding to amino acids 320 - 324 of T10888_PEA_1_P2, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEAlP2, comprising a polypeptide being 15 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP in T10888_PEA-lP2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA_1_P4, comprising a first amino acid 20 sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 25 corresponding to amino acids 1 - 234 of CEA6_HIJMAN, which also corresponds to amino acids 1 - 234 of T10888-PEA-lP4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of 30 T10888_PEA_1_P4, wherein said first and second amino acid sequences are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 103 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEAlP4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 LLLSSQLWPPSASRLECWPGWL in T10888_PEA-lP4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEAlP4, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTESTPFNVAEGKEVLLLAHNLP 10 QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1 - 234 of Q13774, which also corresponds to amino acids 1 - 234 of T10888-PEA_1_P4, and a second amino acid sequence being at least 70%, optionally at least 15 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of T10888_PEA_1_P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of T10888_PEAlP4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL in T10888_PEA_1_P4. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for T10888_PEA-1_P5, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL 30 WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY

GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS

WO 2005/072050 PCT/IB2005/000433 104 YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1 - 320 of CEA6_HIUMAN, which also corresponds to amino acids 1 - 320 of T10888_PEAlP5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 5 having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV corresponding to amino acids 321 - 390 of T10888_PEA-_1P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of T10888_PEAlP5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV in T10888_PEA_1-P5. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA_lP6, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ 20 NDTGFYTLQVIKSDLVNEEATGQFHVY corresponding to amino acids I - 141 of CEA6_1HUMAN, which also corresponds to amino acids 1 - 141 of T10888_PEA_lP6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 REYFIHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI corresponding to amino acids 142 - 183 of T10888_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEALP6, comprising a polypeptide being 30 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072050 PCT/IB2005/000433 105 least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHY-TYQGLDI in T10888-PEA_1_P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T3997 1P6, comprising a first amino acid sequence 5 being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHIEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV 10 LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids I - 276 of VTNCHUMAN, which also corresponds to amino acids 1 - 276 of T3997 1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD corresponding to amino acids 15 277 - 283 of T39971P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 20 90% and most preferably at least about 95% homologous to the sequence TQGVVGD in T39971_P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T3997 _P9, comprising a first amino acid sequence being at least 90 % homologous to 25 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE 30 CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids I - 325 of VTNCHUMAN, which also corresponds to amino acids 1 - 325 of T39971_P9, and a second WO 2005/072050 PCT/IB2005/000433 106 amino acid sequence being at least 90 % homologous to SGMAPRPSLAKKQRFRHJRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357 - 478 of VTNCHUMAN, which also corresponds 5 to amino acids 326 - 447 of T3997 1_P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971P9, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 10 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326 + ((n-2) - x), in which x varies from 0 to n-2. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T3997-P1 1, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV 20 LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1 - 326 of VTNC_HUMAN, which also corresponds to amino acids 1 - 326 of T39971_P11, and a second 25 amino acid sequence being at least 90 % homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442 - 478 of VTNC_-HUMAN, which also corresponds to amino acids 327 - 363 of T39971_P11, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for an edge portion of T3997l_P11, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally WO 2005/072050 PCT/IB2005/000433 107 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino 5 acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P11, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC 10 KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHTGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids I - 326 of 15 Q9BSH7, which also corresponds to amino acids 1 - 326 of T3997l_P11, and a second amino acid sequence being at least 90 % homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442 - 478 of Q9BSH7, which also corresponds to amino acids 327 - 363 of T39971_P11, wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T3997 1_P11, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino 25 acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12, comprising a first amino acid sequence 30 being at least 90 % homologous to

MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC

WO 2005/072050 PCT/IB2005/000433 108 KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSG3KPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1 - 223 of VTNC_-HUMAN, which also corresponds to amino acids I - 223 of 5 T39971P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 - 238 of T39971_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971_P12. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV 20 LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1 - 223 of Q9BSH7, which also corresponds to amino acids 1 - 223 of T39971_P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 25 polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 238 of T39971_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971P12, comprising a polypeptide being at least 30 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about WO 2005/072050 PCT/IB2005/000433 109 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971_P12. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEAlP2, comprising a first amino acid 5 sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMH]EPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ 10 FSKLYPNASQHITPSYNYAPNMDKHVIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYBYTADHGYHGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGF HDKDKECSCRESGYRASRSQRKSQRQFLRNQ 15 GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLI-HPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHQTAPFN corresponding to amino acids 1 - 761 of SUL l_HUMAN, which also corresponds to amino 20 acids 1 - 761 of Z21368_PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI corresponding to amino acids 762 - 790 of Z21368-PEAlP2, wherein said first and second amino acid sequences are contiguous and in a 25 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368-PEAlP2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 PHKYSAHGRTRHFESATRTTNGAQKLSRI in Z21368_PEAlP2.

WO 2005/072050 PCT/IB2005/000433 110 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEAl-P5, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL 5 corresponding to amino acids 1 - 57 of Q7Z2W2, which also corresponds to amino acids 1 - 57 of Z21368_PEALP5, second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITN ESINYFKMSKRtYPHRPVNM SHAAPHGPEDSAPQFSKLYPNASQHTPSYNYAPNM 10 DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVTHTRQTRSLSVEFE 15 GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCN 20 PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139 - 871 of Q7Z2W2, which also corresponds to amino acids 59 - 791 of Z21368_PEA_1_P5, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of Z21368_PEA__P5, comprising a 25 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEA_1_P5): a sequence starting from any of amino acid 30 numbers 57-x to 57; and ending at any of amino acid numbers 59 + ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072050 PCT/IB2005/000433 111 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA_1_P5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 5 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHNIEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD 10 HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV 15 RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME corresponding to amino acids 1 - 751 of Z21368_PEA_1_P5, and a second amino acid sequence being at least 90 20 % homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1 - 40 of AAH12997, which also corresponds to amino acids 752 791 of Z21368_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a head of Z21368_PEA_1_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES 30 INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYiNMLVETGELENTYIIYTAD WO 2005/072050 PCT/IB2005/000433 112 HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE 5 IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLVQLME of 10 Z21368_PEA 1 P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA_ P5, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL 15 corresponding to amino acids 1 - 57 of SUL 1_HUMAN, which also corresponds to amino acids I - 57 of Z21368_PEA_1_P5, and a second amino acid sequence being at least 90 % homologous to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQITPSYNYAPN 20 MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLS\ 25 FEGEIYDINLEEEEELQVLQPRNLKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYK 30 QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138 - 871 WO 2005/072050 PCT/IB2005/000433 113 of SUL1_IHUMAN, which also corresponds to amino acids 58 - 791 of Z21368-PEA.._1P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of Z21368-PEA_1_P5, comprising a 5 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least abott 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid 10 numbers 58 + ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEALP 15, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL 15 QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHTPSYNYAPNMDKHWIMQYTGPMLPIIIMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP 20 GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERG corresponding to amino acids 1 - 416 of SUL IHUMAN, which also corresponds to amino acids I - 416 of Z2136 8 PEA_1_P15. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA_1_P16, comprising a first amino acid 25 sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMIIEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ 30 FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD

SVERLYNMLVETGELENTYIIYTADHGYHGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP

WO 2005/072050 PCT/IB2005/000433 114 GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1 - 397 of SULl_HUMAN, which also corresponds to amino acids I - 397 of Z21368-PEA_1_P16, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 5 homologous to a polypeptide having the sequence CVIVPPLSQPQIH corresponding to amino acids 398 - 410 of Z21368_PEA_1_P16, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA-1_P16, comprising a polypeptide being 10 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH in Z21368_PEA_1_P16. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368-PEA_ 1_P22, comprising a first amino acid 15 sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMILTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1 - 188 of SULl_-IUMAN, which also 20 corresponds to amino acids 1 - 188 of Z21368_PEA_1_P22, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF corresponding to amino acids 189 - 210 of Z21368_PEA_1_P22, wherein said first and second amino acid sequences are contiguous and in 25 a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA_1_P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 ARYDGDQPRCAPRPRGLSPTVF in Z21368_PEA_1_P22.

WO 2005/072050 PCT/IB2005/000433 115 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEAl-P23, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL 5 QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1 - 137 of Q7Z2W2, which also corresponds to amino acids I - 137 of Z21368_PEA-lP23, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 GLLHRLNH corresponding to amino acids 138 - 145 of Z21368_PEA_1_P23, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEAlP23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 15 least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA_1 P23, comprising a first amino acid sequence being at least 90 % homologous to 20 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATF[NAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids I - 137 of SUL 1-HUMAN, which also corresponds to amino acids 1 - 137 of Z21368-PEA_1_P23, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 25 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH corresponding to amino acids 138 - 145 of Z21368_PEA_1_P23, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEAlP23, comprising a polypeptide being 30 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072050 PCT/IB2005/000433 116 least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832P5, comprising a first amino acid sequence 5 being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12 - 55 of GILTHUMAN, which also corresponds to amino acids 1 - 44 of T59832P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 10 polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG corresponding to amino acids 45 - 189 of T59832P5, wherein said first and second amino acid-sequences are contiguous and in a 15 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832-P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG in T59832_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7, comprising a first amino acid sequence 25 being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQ LYAPGLSPDTIM ECAMGDRGMQLMIANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 12 30 - 223 of GILTHUMAN, which also corresponds to amino acids 1 - 212 of T59832_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, WO 2005/072050 PCT/IB2005/000433 117 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 213 - 238 of T59832_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832-P7, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 15 QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1 - 212 of BAC98466, which also corresponds to amino acids 1 - 212 of T59832_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 20 the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 213 - 238 of T59832_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7, comprising a polypeptide being at least 25 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7, comprising a first amino acid sequence 30 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072050 PCT/IB2005/000433 118 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids 1 - 90 of T59832_P7, and a second amino acid sequence being at least 90 % homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC 5 MEEFEDMERSLPLCLQLYAPGLSPDTIECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRLFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1 - 148 of BAC85622, which also corresponds to amino acids 91 - 238 of T59832_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a head of T59832_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P7. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 20 QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMRSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids I - 212 of Q8WU77, which also corresponds to amino acids 1 - 212 of T59832P7, and a-second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 25 the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 213 - 238 of T59832P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832P7, comprising a polypeptide being at least 30 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about WO 2005/072050 PCT/IB2005/000433 119 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence 5 being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVNMELNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHIE corresponding to amino acids 12 - 21'4 of 10 GIILTHUMAN, which also corresponds to amino acids 1 - 203 of T59832_P9, and a second amino acid sequence being at least 7 0%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to amino acids 204 - 244 of T59832_P9, wherein said first and second amino acid sequences are 15 contiguous and in a sequential order. According to preferred embodiments of the present invertion, there is provided an isolated polypeptide encoding for a tail of T59832_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA 25 PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1 - 203 of BAC98466, which also corresponds to amino acids I - 203 of T59832P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 30 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to WO 2005/072050 PCT/IB2005/000433 120 amino acids 204 - 244 of T59832P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9, comprising a polypeptide being at least 5 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence 10 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids 1 - 90 of T59832P9, second amino acid sequence being at least 90 % homologous to 15 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1 - 113 of BAC85622, which also corresponds to amino acids 91 203 of T59832_P9, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 20 homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to amino acids 204 - 244 of T59832P9, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a head of T59832P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P9. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832P9, comprising a polypeptide being at least WO 2005/072050 PCT/IB2005/000433 121 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM 10 ECAMGDRGMQLMIHANAQRTDALQPPHE corresponding to amino acids 1 - 203 of Q8WUJ77, which also corresponds to amino acids 1 - 203 of T59832P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to 15 amino acids 204 - 244 of T59832P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 20 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832._P12, comprising a first amino acid sequence being at least 90 % homologous to 25 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 12 - 141 of GILTHUMAN, which also corresponds to amino acids 1 - 130 of T59832_P12, and a second amino acid sequence being at least 90 % homologous to 30 CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173 - 261 of WO 2005/072050 PCT/IB2005/000433 122 GILTHUMAN, which also corresponds to amino acids 131 - 219 of T59832_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832P12, comprising a 5 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino 10 acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids 1 - 90 of T59832P 12, second amino acid sequence being at least 90 % homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids I - 40 of BAC85622, which also corresponds to amino acids 91 - 130 of T59832P12, 20 third amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 72 - 122 of BAC85622, which also corresponds to amino acids 131 - 181 of T59832_P12, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 25 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 182 - 219 of T59832P12, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a head of T59832P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072050 PCT/IB2005/000433 123 about 90% and most prefrably at least about 95% homologous to the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P12. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for an edge portion of T59832_P12, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a 10 sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832P 12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 15 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK in T59832_P12. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P2, comprising a first amino acid sequence being at least 90 % homologous to 20 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMELNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1 - 130 of Q8WU77, which also corresponds to amino acids I - 130 of T59832_P12, and a second amino acid sequence being at least 90 % homologous to 25 CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of Q8WU77, which also corresponds to amino acids 131 - 219 of T59832_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for an edge portion of T59832_P12, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally WO 2005/072050 PCT/IB2005/000433 124 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino 5 acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832P 18, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino 10 acids 12 - 55 of GILTHUMAN, which also corresponds to amino acids I - 44 of T59832_P18, and a second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGK.PLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173 - 261 of GILTHUMAN, which also corresponds to amino acids 45 - 133 of T59832_P18, wherein said 15 first and second amino acid sequences are contiguous and in a sequential order. According to preferred-embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more 20 preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for T59832P 18, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1 - 44 of Q8WU77, which also corresponds to amino acids 1 - 44 of T59832_P18, and a second amino acid sequence being at least 90 % homologous to 30 CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of WO 2005/072050 PCT/IB2005/000433 125 Q8WU77, which also corresponds to amino acids 45 - 133 of T59832_P18, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18, comprising a 5 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid 10 numbers 45+ ((r-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNK corresponding to amino 15 acids 1 - 44 of Q8NEI4, which also corresponds to amino acids 1 - 44 of T59832 P18, and a second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of Q8NEI4, which also corresponds to amino acids 45 - 133 of T59832_P18, wherein said first and 20 second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more 25 preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for HUMGRP5E-P4, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 126 MRGSELPLVLLALVLCLAPRGRA VPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEA.ARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1 - 127 of GRP_HIJMAN, which also corresponds to amino acids 1 - 127 of HUMGRP5EP4, and a second amino acid sequence 5 being at least 90 % homologous to GSQREGRNPQLNQQ corresponding to amino acids 135 148 of GRP_HUMqAN, which also corresponds to amino acids 128 - 141 of HUMGRP5EP4, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMGRP5EP4, comprising a 10 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KG, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino 15 acid numbers 128 + ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HU-RMGRP5E_P5, comprising a first amino acid sequence being at least 90 % homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHW AVGHLMGKKSTG 20 ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1 - 127 of GRPHUMAN, which also corresponds to amino acids 1 - 127 of HUMGRP5EP5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 DSLLQVLNVKEGTPS corresponding to amino acids 128 - 142 of HUMGRP5EP5, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMGRP5E_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 30 about 90% and most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS in HUMGRP5EP5.

WO 2005/072050 PCT/IB2005/000433 127 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA-lP4, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ 5 PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTT RSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP corresponding to amino acids 1 - 146 of KLKAHUMAN, which also corresponds to amino acids 1 - 146 of AA 155578_PEA_1_P4, and a second amino acid sequence being at least 90 % homologous to YNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGIL 10 SWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 184 - 276 of KLKA_-HUMAN, which also corresponds to amino acids 147 - 239 of AA155578_PEAlP4, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA-lP4, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PY, having a 20 structure as follows: a sequence starting from any of amino acid numbers 146-x to 146; and ending at any of amino acid numbers 147+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to 25 MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1 - 29 of KLKAHUMAN, which also corresponds to amino acids I - 29 of AA155578_PEA_1_P6, and a second amino acid sequence being at least 90 % homologous to VKYNIKGLTCSSITILSPKECEVFYTGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 182 30 276 of KLKA_HUMAN, which also corresponds to amino acids 30 - 124 of WO 2005/072050 PCT/IB2005/000433 128 AA155578_PEA-lP6, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of AA155578_PEAlP6, 5 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise WV, having a structure as follows: a sequence starting from any of amino acid numbers 29-x to 29; and ending 10 at any of amino acid numbers 30+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA-lP8, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1 - 29 of 15 KLKA_HUMAN, which also corresponds to amino acids 1 - 29 of AA155578_PEAl-P8, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GHCGLE corresponding to amino acids 30 - 35 of AA155578-PEA__P8, wherein said first and second amino acid sequences are contiguous and 20 in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of AA155578_PEA_1_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 GHCGLE in AA155578_PEA_1_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578PEAlP9, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ 30 PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK corresponding to amino acids 1 - 90 of KLKAHUIAN, which also corresponds to amino acids I - 90 of AA155578-PEA_1_P9.

WO 2005/072050 PCT/IB2005/000433 129 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSENA78_P2, comprising a first amino acid sequence being at least 90 % homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP 5 KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1 - 81 of SZ05_HUMAN, which also corresponds to amino acids 1 - 81 of HSENA78_P2. According to preferred embodiments of the present invention, there is provided an isola ted chimeric polypeptide encoding for T94936_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to 10 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVWIHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL corresponding to amino acids 1 - 150 of Q8TD06, which also corresponds to amino acids 1 - 150 of T94936_PEA_1_P2. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for T94936_PEA_1_P3, comprising a first amino acid sequence being at least 90 % homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFV corresponding to amino acids 1 - 122 of Q8TD06, which also corresponds to amino 20 acids 1 - 122 of T94936_PEA._LP3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMYVISFHQIYKISRNQHSCFYF corresponding to amino acids 123 - 145 of T94936_PEA_1_P3, wherein said first and second amino acid sequences are contiguous and in a 25 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T94936_PEAlP3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 GMYVISFHQIYKISRNQHSCFYF in T94936_PEA_1-P3.

WO 2005/072050 PCT/IB2005/000433 130 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA_1_P10, comprising a first amino acid sequence being at least 90 % homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII 5 TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids I 95 of SZ14_HUMAN, which also corresponds to amino acids 1 - 95 of Z41644_PEA_1_PlO, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to 10 amino acids 96 - 123 of Z41644_PEA_1_Pl0, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA_1_Pl0, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 15 least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA-__PlO. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA_1_Pl0, comprising a first amino acid sequence being at least 90 % homologous to 20 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13 107 of Q9NS21, which also corresponds to amino acids 1 - 95 of Z41644_PEA_1_P10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 25 having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to amino acids 96 - 123 of Z41644_PEA_1-P1O, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA_1_P10, comprising a polypeptide being 30 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072050 PCT/IB2005/000433 131 least about 90% and most preferably at least about 95% horiologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA_1_Pl0. According to preferred embodiments of the preser invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA_1_P10, comprising a first amino acid 5 sequence being at least 90 % homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13 107 of AAQ89265, which also corresponds to amino acids 1 - 95 of Z41644_PEA-LP10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 10 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to amino acids 96 - 123 of Z41644-PEA_LP1O, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of Z41644_PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA_1_PlO. According to preferred embodiments of the present invention, there is provided an isolated 20 oligonucleotide, comprising an amplicon selected from the group consisting of SEQ ID NOs: 891 or 894. According to preferred embodiments of the present invention, there is provided a primer pair, comprising a pair of isolated oligonucleotides capable of amplifying the above. Optionally, the pair of isolated oligonucleotides is selected from the group consisting of: SEQ 25 NOs 889 and 890; or 892 and 893. According to preferred embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence as described herein. Optionally, the epitope may comprise a tail, head, or edge portion as described herein. According to preferred embodiments of the present invention, the antibody is capable of 30 differentiating between a splice variant having said epitope and a corresponding known protein.

WO 2005/072050 PCT/IB2005/000433 132 According to preferred embodiments of the present invention, there is provided an kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant as described herein. Optionally, the kit comprises a NAT-based technology. Preferably, the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid 5 sequence as described herein. Optionally, the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence as described herein. Optionally, the kit comprises an antibody as described herein. Preferably, the kit further comprises at least one reagent for performing an ELISA or a Western blot. 10 According to preferred embodiments of the present invention, there is provided a method for detecting breast cancer, comprising detecting overexpression of a splice variant as described herein. Optionally detecting overexpression is performed with a NAT-based technology. Preferably, detecting overexpression is performed with an immunoassay. More preferably, the 15 immunoassay comprises an antibody as described herein. According to preferred embodiments of the present invention, there is provided a biomarker capable of detecting breast cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof. 20 According to preferred embodiments of the present invention, preferably any of the above nucleic acid and/or amino acid sequences further comprises any sequence having at least about 70%, preferably at least about 80%, more preferably at least about 90%, most preferably at least about 95% homology thereto. Unless otherwise noted, all experimental data relates to variants of the present invention, 25 named according to the segment being tested (as expression was tested through RT-PCR as described). All nucleic acid sequences aid/or amino acid sequences shown herein as embodiments of the present invention relate to their isolated form, as isolated polynucleotides (including for all transcripts), oligonucleotides (including for all segments, amplicons and primers), peptides 30 (including for all tails, bridges, insertions or heads, optionally including other antibody epitopes as described herein) and/or polypeptides (including for all proteins). It should be noted that WO 2005/072050 PCT/IB2005/000433 133 oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally be used interchangeably. Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The 5 following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of these are hereby incorporated by reference 10 as if fully set forth herein. As used herein, the following terms have the meanings ascribed to them unless specified otherwise. BRIEF DESCRIPTION OF DRAWINGS Figure 1 is schematic summary of cancer biomarkers selection engine and the wet 15 validation stages. Figure 2. Schematic illustration, depicting grouping of transcripts of a given cluster based on presence or absence of unique sequence regions. Figure 3 is schematic summary of quantitative real-time PCR analysis. Figure 4 is schematic presentation of the oligonucleotide based microarray fabrication. 20 Figure 5 is schematic summary of the oligonucleotide based microarray experimental flow. Figure 6 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma. 25 Figure 7 is a histogram showing expression of the CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888) transcripts, which are detectable by amplicon as depicted in sequence name T10888 juncl 1-17, in normal and cancerous breast tissues. Figure 8 is a histogram showing the expression of CEA6._HUMAN Carcinoembryonic 30 antigen-related cell adhesion molecule 6 T10888 transcripts which are detectable by amplicon as depicted in sequence name TI0888juncl 1-17 in different normal tissues.

WO 2005/072050 PCT/IB2005/000433 134 Figure 9 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster T39971, demonstrating overexpression in liver cancer, lung malignant tumors and pancreas carcinoma. Figure 10 is a histogram showing the expression of of VTNC_HUMAN vitronectin 5 (serum spreading factor, somatomedin B, complement S-protein) T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971 junc23-33 in normal and cancerous breast tissues. Figure 11 is a histogram showing the expression of VTNCHUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARM1 (T23434), 10 T39971 transcripts, which are detectable by amplicon as depicted in sequence name T3997ljunc23-33, in different normal tissues. Figure 12 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster Z21368, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. 15 Figure 13 is a histogram showing the expression of SULlHUIAN - Extracellular sulfatase Sulf- 1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39, in normal and cancerous breast tissues. Figure 14 is a histogram showing the expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- IZ21368 transcripts, which are detectable by amplicon as depicted in sequence 20 name Z21368seg39, in different normal tissues. Figure 15 is a histogram showing the expression of SUL _-HUMAN - Extracellular sulfatase Sulf- I Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368junc17-21 in normal and cancerous breast tissues. Figure 16 is a histogram showing the expression of SUL1_-HJMAN - Extracellular 25 sulfatase Sulf- 1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368juncl7-21, in different normal tissues. Figure 17 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T59832, demonstrating overexpression in brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

WO 2005/072050 PCT/IB2005/000433 135 Figure 18 is a histogram showing low over expression observed for cluster T59832, amplicon name: T59832 junc6-25-26, in one experiment carried out with breast cancer samples panel. Figure 19 is a histogram showing the expression of GRPHUMAN - gastrin-releasing 5 peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted insequence name HUTvIGRP5Ejunc3-7 in normal and cancerous breast tissues. Figure 20 is a histogram showing the expression of GRPHUMAN - gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7, in different normal tissues. 10 Figure 21 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster AA155578, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. Figure 22 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster HSENA78, demonstrating overexpression in epithelial malignant tumors and lung 15 malignant tumors. Figure 23 is a histogram showing the expression of Homo sapiens breast cancer membrane protein 11 (BCMP1 1) T94936 transcripts which are detectable by amplicon as depicted in sequence name T94936 segl4 in nonrinal and cancerous Breast tissues. Figure 24 is a histogram showing Cancer and cell- line vs. normal tissue expression for 20 Cluster Z41644, demonstrating overexpression in lung malignant tumors, breast malignant tumors and pancreas carcinoma. Figure 25 is a histogram showing Cancdr and cell-line vs. normal tissue expression for Cluster M85491, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues. 25 Figure 26 is a histogram showing the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in normal and cancerous breast tissues. Figure 27 is a histogram showing the expression of Ephrin type-B receptor 2 precursor 30 M85491 transcripts, which are detectable by amplicon as depicted in sequence name M85491 seg24, in different normal tissues.

WO 2005/072050 PCT/IB2005/000433 136 Figure 28 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster HSSTROL3, demonstrating overexpression in transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. Figure 29A is a histogram showing the expression of Expression of Stromelysin-3 5 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) SL-3 HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 in normal and cancerous breast tissues. Figure 29B is a histogram showing the expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMIP- 11) (ST3) (SL-3) HSSTROL3 transcripts, which 10 are detectable by amplicon as depicted in sequence name HSSTROL3 seg24, in different normal tissues. Figures 30A-30C shows histograms showing over expression of various Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples. Figure 31 is a histogram showing Cancer and cell- line vs. normal tissue expression for 15 Cluster R75793, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues. Figure 32 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster HUMCA1XIA, demonstrating overexpression in bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant 20 tumors. Figure 33 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster R20779, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors. Figure 34 is a histogram showing Cancer and cell- line vs. normal tissue expression for 25 Cluster HSS 1 OOPCB, demonstrating overexpression in a mixture of malignant tumors from different tissues. Figure 35 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster HSCOC4, demonstrating overexpression in brain malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and 30 prostate cancer.

WO 2005/072050 PCT/IB2005/000433 137 Figure 36 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMvITREFAC, demonstrating overexpression in a mixture of malignant-tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer. Figure 37 is a histogram showing Cancer and cell- line vs. normal tissue expression for 5 Cluster HUMOSTRO, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors, breast malignant tumors, ovarian carcinoma and skin malignancies. Figure 38 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster R 11723, demonstrating overexpression in epithelial malignant tumors, a mixture of 10 malignant tumors from different tissues and kidney malignant tumors. Figure 39 is a histogram showing the expression of of RI 1723 transcripts which are detectable by amplicon as depicted in sequence name RI 1723 segl3 in normal and cancerous breast tissues. Figure 40 is a histogram showing the expression of RI 1723 transcripts, which are 15 detectable by amplicon as depicted in sequence name R 11723seg13, in different normal tissues. Figures 41A and B are histograms showing the expression of RI 1723 transcripts, which are detectable by amplicon as depicted in sequence name R 11723 junc I1-18 in normal and cancerous breast tissues (Figure 41A) or on a panel of normal tissues (Figure 41B). Figure 42 is a histogram showing Cancer and cell- line vs. normal tissue expression for 20 Cluster T46984, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, ovarian carcinoma and pancreas carcinoma. Figure 43 is a histogram 'showing Cancer and cell- line vs. normal tissue expression for Cluster HSMUC I A, demonstrating overexpression in a mixture of malignant tumors from 25 different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer. Figures 44-47 are histograms showing the combined expression of 8 sequences (TIO888segl l-17, HUMGR5E junc3-7, HSSTROL3seg24, T94936 Seg 14, Z21368 seg39, Z21368junc17-21 T59832jun6-25-26 and M85491seg24) in normal and cancerous breast tissues.

WO 2005/072050 PCT/IB2005/000433 138 Figure 48 is a histogram showing Cancer and cell- line vs. normal tissue expression for Cluster HSU33147, demonstrating overexpression in a mixture of malignant tumors from different tissues. 5 DESCRIPTION OF PREFERRED EMBODIMENTS The present invention is of novel markers for breast cancer that are both sensitive and accurate. Furthermore, at least certain of these markers are able to distinguish between different stages of breast cancer, such as 1. Ductal carcinoma (in-situ, invasive) 2. Lobular carcinoma (is situ, invasive) 3. inflammatory breast cancer 4. Mucinous carcinoma 5. Tubular carcinoma 6. 10 Paget's disease of nipple, alone or in combination; or one of the indicative conditions described above. The markers of the present invention, alone or in combination, can be used for prognosis, prediction, screening, early diagnosis, staging, therapy selection and treatment ' monitoring of breast cancer. For example, optionally and preferably, these markers may be used 15 for staging breast cancer and/or monitoring the progression of the disease. Furthermore, the markers of the present invention, alone or in combination, can be used for detection of the source of metastasis found in anatomical places other then breast. Also, one or more of the markers may optionally be used in combination with one or more other breast cancer markers (other than those described herein). 20 Biomolecular sequences (amino acid and/or nucleic acid sequences) uncovered using the methodology of the present invention and described herein can be efficiently utilized as tissue or pathological markers and/or as drugs or drug targets for treating or preventing a disease. These markers are specifically released to the bloodstream under conditions of breast cancer (or one of the above indicative conditions), and/or are otherwise expressed at a much 25 higher level and/or specifically expressed in breast cancer tissue or cells, and/or tissue or cells under one of the above indicative conditions. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer and/or a condition that it is indicative of a higher risk for breast cancer. 30 The present invention therefore also relates to diagnostic assays for breast cancer and/or an indicative condition, and methods of use of such markers for detection of breast cancer WO 2005/072050 PCT/IB2005/000433 139 and/or an indicative condition, optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample. According to a preferred embodiment of the present invention, use of the marker optionally and preferably permits a non-cancerous breast disease state to be distinguished from 5 breast cancer and/or an indicative condition. A non limiting example of a non-cancerous breast disease state includes breast fibrosis and/or cysts. According to another preferred embodiment of the present invention, use of the marker optionally and preferably permits an indicative condition to be distinguished from breast cancer. In another embodiment, the present invention relates to bridges, tails, heads and/or 10 insertions, and/or analogs, homologs and derivatives of such peptides. Such bridges, tails, heads and/or insertions are described in greater detail below with regard to the Examples. As used herein a "tail" refers to a peptide sequence at the end of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a tail may optionally be considered as a chimera, in that at least a first portion of the 15 splice variant is typically highly homologous (often 100% identical) to a portion of the corresponding known protein, while at least a second portion of the variant comprises the tail. As used herein a "head" refers to a peptide sequence at the beginning of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a head may optionally be considered as a chimera, in that at least a first 20 portion of the splice variant comprises the head, while at least a second portion is typically highly homologous (often 100% identical) to a portion of the corresponding known protein. As used herein "an edge portion" refers to a connection between two portions of a splice variant according to the present invention that were not joined in the wild type or known protein. An edge may optionally arise due to a join between the above "known protein" portion 25 of a variant and the tail, for example, and/or may occur if an internal portion of the wild type sequence is no longer present, such that two portions of the sequence are now contiguous in the splice variant that were not contiguous in the known protein. A "bridge" may optionally be an edge portion as described above, but may also include a join between a head and a "known protein" portion of a variant, or a join between a tail and a "known protein" portion of a variant, 30 or a join between an insertion and a "known protein" portion of a variant. Optionally and preferably, a bridge between a tail or a head or a unique insertion, and a WO 2005/072050 PCT/IB2005/000433 140 "known protein" portion of a variant, comprises at least about 10 amino acids, more preferably at least about 20 amino acids, most preferably at least about 30 amino acids, and even more preferably at least about 40 amino acids, in which at least one amino acid is from the tail/head/insertion and at least one amino acid is from the "known protein" portion of a variant. 5 Also optionally, the bridge may comprise any number of amino acids from about 10 to about 40 amino acids (for example, 10, 11, 12, 13.. .37, 38, 39, 40 amino acids in length, or any number in between). It should be noted that a bridge cannot be extended beyond the length of the sequence in either direction, and it should be assumed that every bridge description is to be read in such 10 manner that the bridge length does not extend beyond the sequence itself. Furthermore, bridges are described with regard to a sliding window in certain contexts below. For example, certain descriptions of the bridges feature the following format: a bridge between two edges (in which a portion of the known protein is not present in the variant) may optionally be described as follows: a bridge portion of CONTIG-NAMEPI (representing the 15 name of the protein), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at bast two amino acids comprise XX (2 amino acids in the center of the bridge, one from each end of the edge), having a 20 structure as follows (numbering according to the sequence of CONTIG-NAME-Pl): a sequence starting from any of amino acid numbers 49-x to 49 (for example); and ending at any of amino acid numbers 50 + ((n-2) - x) (for example), in which x varies from 0 to n-2. In this example, it should also be read as including bridges in which n is any number of amino acids between 10-50 amino acids in length. Furthermore, the bridge polypeptide cannot extend beyond the sequence, 25 so it should be read such that 49-x (for example) is not less than 1, nor 50 + ((n-2) - x) (for example) greater than the total sequence length. In another embodiment, this invention provides antibodies specifically recognizing the splice variants and polypeptide fragments thereof of this invention. Preferably such antibodies differentially recognize splice variants of the present invention but do not recognize a 30 corresponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below).

WO 2005/072050 PCT/IB2005/000433 141 In another embodiment, this invention provides an isolated nucleic acid molecule encoding for a splice variant according to the present invention, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an isolated nucleic acid molecule, having a 5 nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this invention. In another embodiment, this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention. 10 In another embodiment, this invention provides a method for detecting a splice variant according to the present invention in a biological sample, comprising: contacting a biological sample with an antibody specifically recognizing a splice variant according to the present invention under conditions whereby the antibody specifically interacts with the splice variant in the biological sample but do not recognize known corresponding proteins (wherein the known 15 protein is discussed with regard to its splice variant(s) in the Examples below), and detecting said interaction; wherein the presence of an interaction correlates with the presence of a splice variant in the biological sample. In another embodiment, this invention provides a method for detecting a splice variant nucleic acid sequences in a biological sample, comprising: hybridizing the isolated nucleic acid 20 molecules or oligonucleotide fragments of at least about a minimum length to a nucleic acid material of a biological sample and detecting a hybridization complex; wherein the presence of a hybridization complex correlates with the presence of a splice variant nucleic acid sequence in the biological sample. According to the present invention, the splice variants described herein are non-limiting 25 examples of markers for diagnosing breast cancer and/or an indicative condition. Each splice variant marker of the present invention can be used alone or in combination, for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of progression, therapy selection and treatment monitoring of breast cancer and/or an indicative condition, including a transition from an indicative condition to breast cancer.

WO 2005/072050 PCT/IB2005/000433 142 According to optional but preferred embodiments of the present invention, any marker according to the present invention may optionally be used alone or combination. Such a combination may optionally comprise a plurality of markers described herein, optionally including any subcombination of markers, and/or a combination featuring at least one other 5 marker, for example a known marker. Furthermore, such a combination may optionally and preferably be used as described above with regard to determining a ratio between a quantitative or semi-quantitative measurement of any marker described herein to any other marker described herein, and/or any other known marker, and/or any other marker. With regard to such a ratio between any marker described herein (or a combination thereof) and a known marker, more 10 preferably the known marker comprises the "known protein" as described in greater detail below with regard to each cluster or gene. According to other preferred embodiments of the present invention, a splice variant protein or a fragment thereof, or a splice variant nucleic acid sequence or a fragment thereof, may be featured as a biomarker for detecting breast cancer and/or an indicative condition, such 15 that a biomarker may optionally comprise any of the above. According to still other preferred embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence corresponding to a splice variant protein as described herein. Any oligopeptide or peptide relating to such an amino acid sequence or fragment thereof may optionally also 20 (additionally or alternatively) be used as a biomarker, including but not limited to the unique amino acid sequences of these proteins that are depicted as tails, heads, insertions, edges or bridges. The present invention also optionally encompasses antibodies capable of recognizing, and/or being elicited by, such oligopeptides or peptides. The present invention also optionally and preferably encompasses any nucleic acid 25 sequence or fragment thereof, or amino acid sequence or fragment thereof, corresponding to a splice variant of the present invention as described above, optionally for any application. Non-limiting examples of methods or assays are described below. The present invention also relates to kits based upon such diagnostic methods or assays. 30 Nucleic acid sequences and Oligonucleotides WO 2005/072050 PCT/IB2005/000433 143 Various embodiments of the present invention encompass nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or 5 more nucleotides, either naturally occurring or artificially induced, either randomly or in a targeted fashion. The present invention encompasses nucleic acid sequences described herein; fragments thereof, sequences hybridizable therewith, sequences homologous thereto [e.g., at least 50 %, at least 55 %, at least 60%, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at 10 least 95 % or more say 100 % identical to the nuc leic acid sequences set forth below], sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion. The present invention also encompasses homologous nucleic acid sequences (i.e., which form a part of a polynucleotide 15 sequence of the present invention) which include sequence regions unique to the polynucleotides of the present invention. In cases where the polynucleotide sequences of the present invention encode previously unidentified polypeptides, the present invention also encompasses novel polypeptides or portions thereof, which are encoded by the isolated polynucleotide and respective nucleic acid fragments 20 thereof described hereinabove. A "nucleic acid fragment" or an "oligonucleotide" or a "polynucleotide" are used herein interchangeably to refer to a polymer of nucleic acids. A polynucleotide sequence of the present invention refers to a single or double stranded nucleic acid sequences which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a 25 genomic polynucleotide sequence and/or a composite polynucleotide sequences (e.g., a combination of the above). As used herein the phrase "complementary polynucleotide sequence" refers to a sequence, which results from reverse transcription of messenger RNA using a reverse transcriptase or any other RNA dependent DNA polymerase. Such a sequence can be 30 subsequently amplified in vivo or in vitro using a DNA dependent DNA polymerase.

WO 2005/072050 PCT/IB2005/000433 144 Ai used herein the phrase "genomic polynucleotide sequence" refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosomvie. As used herein the phrase "composite polynucleotide sequence" refers to a sequence, 5 which is composed of genomic and cDNA sequences. A composite sequence can include some exonal sequences required to encode the polypeptide of the present invention, as well as some intronic sequences interposing therebetween. The intronic sequences can be of any source, including of other genes, and typically will include conserved splicing signal sequences. Such intronic sequences may further include cis acting expression regulatory elements. 10 Preferred embodiments of the present invention encompass oligonucleotide probes. An example of an oligonucleotide probe which can be utilized by the present invention is a single stranded polynucleotide which includes a sequence complementary to the unique sequence region of any variant according to the present invention, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion 15 according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein). Alternatively, an oligonucleotide probe of the present invention can be designed to hybridize with a nucleic acid sequence encompassed by any of the above nucleic acid sequences, 20 particularly the portions specified above, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein). Oligonucleotides designed according to the teachings of the present invention can be 25 generated according to any oligonucleotide synthesis method known in the art such as enzymatic synthesis or solid phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as 30 detailed in, for example, "Molecular Cloning: A laboratory Manual" Sambrook et al., (1989); "Current Protocols in Molecular Biology" Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et WO 2005/072050 PCT/IB2005/000433 145 al., "Current Protocols in Molecular Biology", John Wiley and Sons, Baltimore, Maryland (1989); Perbal, "A Practical Guide to Molecular Cloning", John Wiley & Sons, New York (1988) and "Oligonucleotide Synthesis" Gait, M. J., ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and purification by for 5 example, an automated trityl-on method or HPLC. Oligonucleotides used according to this aspect of the present invention are those having a length selected from a range of about 10 to about 200 bases preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. Preferably, the oligonucleotide of the present invention features at least 17, at least 18, at least 10 19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases specifically hybridizable with the biomarkers of the present invention. The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3' to 5' phosphodiester linkage. Preferably used oligonucleotides are those modified at one or more of the backbone, 15 internucleoside linkages or bases, as is broadly described hereinunder. Specific examples of preferred oligonucleotides useful according to this aspect of the present invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone, as disclosed in U.S. Pat. NOs: 4,469,863; 4,476,301; 20 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466, 677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050. Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, 25 methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside 30 units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms can also be used.

WO 2005/072050 PCT/IB2005/000433 146 Alternatively, modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl intemucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having 5 morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, 0, S and CH 2 component parts, as 10 disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623, 070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439. Other oligonucleotides which can be used according to the present invention, are those 15 modified in both sugar and the intemucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for complementation with the appropriate polynucleotide target. An example for such an oligonucleotide mimetic, includes peptide nucleic acid (PNA). United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of 20 which is herein incorporated by reference. Other backbone modifications, which can be used in the present invention are disclosed in U.S. Pat. No: 6,303,374. Oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, "unmodified" or "natural" bases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). 25 Modified bases include but are not limited to other synthetic and natural bases such as 5 methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil 30 (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8 substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5- WO 2005/072050 PCT/IB2005/000433 147 substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8 azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 5 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6 1.2 *C and are presently preferred base substitutions, even more particularly when combined with 2'-0-methoxyethyl sugar modifications. Another modification of the oligonucleotides of the invention involves chemically 10 linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-S tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac- glycerol or triethylammonium 1,2-di-O-hexadecyl-rac 15 glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, as disclosed in U.S. Pat. No: 6,303,374. It is not necessary for all positions in a given oligonucleotide molecule to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in 20 a single compound or even at a single nucleoside within an oligonucleotide. It will be appreciated that oligonucleotides of the present invention may include further modifications for more efficient use as diagnostic agents and/or to increase bioavailability, therapeutic efficacy and reduce cytotoxicity. To enable cellular expression of the polynucleotides of the present invention, a nucleic 25 acid construct according to the present invention may be used, which includes at least a coding region of one of the above nucleic acid sequences, and further includes at least one cis acting regulatory element. As used herein, the phrase "cis acting regulatory element" refers to a polynucleotide sequence, preferably a promoter, which binds a trans acting regulator and regulates the transcription of a coding sequence located downstream thereto. 30 Any suitable promoter sequence can be used by the nucleic acid construct of the present invention.

WO 2005/072050 PCT/IB2005/000433 148 Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed. Examples of cell type-specific and/or tissue specific promoters include promoters such as albumin that is liver specific, lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell 5 receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], neuron-specific promoters such as the neurofilament promoter [Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477], pancreas-specific promoters [Edlunch et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). 10 The nucleic acid construct of the present invention can further include an enhancer, which can be adjacent or distant to the promoter sequence and can function in up regulating the transcription therefrom. The nucleic acid construct of the present invention preferably further includes an appropriate selectable marker and/or an origin of replication. Preferably, the nucleic acid 15 construct utilized is a shuttle vector, which can propagate both in E. coli (wherein the construct comprises an appropriate selectable marker and origin of replication) and be compatible for propagation in cells, or integration in a gene and a tissue of choice. The construct according to the present invention can be, for example, a plasmid, a bacmid, a phagemid, a cosmid, a phage, a virus or an artificial chromosome. 20 Examples of suitable constructs include, but are not limited to, pcDNA3, pcDNA3.1 (+/-), pGL3, PzeoSV2 (+/-), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available from Invitrogen Co. (www.invitrogen.com). Examples of retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif., includingRetro-X vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and the trasgene 25 is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also included such as pBabe, where the transgene will be transcribed from the 5'LTR promoter. Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno associated virus (AAV) and lipid-based systems. Useful lipids for lipid- mediated transfer of the 30 gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most WO 2005/072050 PCT/IB2005/000433 149 preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter/enhancer or locus-defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector 5 constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present h the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the 10 polypeptide variants of the present invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' LTR or a portion thereof. Other vectors can be used that are non-viral, such as cationic lipids, 15 polylysine, and dendrimers. Hybridization assays Detection of a nucleic acid of interest in a biological sample may optionally be effected by hybridization-based assays using an oligonucleotide probe (non-limiting examples of probes 20 according to the present invention were previously described). Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase protection, in-situ hybridization, primer extension, Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are described in greater detail below). More recently, PNAs have been described (Nielsen et al. 1999, Current 25 Opin. Biotechnol. 10:71-75). Other detection methods include kits containing probes on a dipstick setup and the like. Hybridization based assays which allow the detection of a variant of interest (i.e., DNA or RNA) in a biological sample rely on the use of oligonucleotides which can be 10, 15, 20, or 30 to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to 50 nucleotides 30 long.

WO 2005/072050 PCT/IB2005/000433 150 Thus, the isolated polynucleotides (oligonucleotides) of the present invention are preferably hybridizable with any of the herein described nucleic acid sequences under moderate to stringent hybridization conditions. Moderate to stringent hybridization conditions are characterized by a hybridization 5 solution such as containing 10 % dextrane sulfate, 1 M NaCl, I % SDS and 5 x 106 cpm 3p labeled probe, at 65 'C, with a final wash solution of 0.2 x SSC and 0.1 % SDS and final wash at 65'C and whereas moderate hybridization is effected using a hybridization solution containing 10 % dextrane sulfate, I M NaCl, I % SDS and 5 x 106 cpm 32 P labeled probe, at 65 'C, with a final wash solution of 1 x SSC and 0.1 % SDS and final wash at 50 'C. 10 More generally, hybridization of short nucleic acids (below 200 bp in length, e.g. 17-40 bp in length) can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency; (i) hybridization solution of 6 x SSC and 1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 pg/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature 15 of 1 - 1.5 'C below the Tn, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 n]M EDTA (pH 7.6), 0.5 % SDS at I - 1.5 'C below the Tm; (ii) hybridization solution of 6 x SSC and 0.1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 pg/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature of 2 - 2.5 'C below the Tm, final wash solution of 3 M TMACI, 0.01 20 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS at 1 - 1.5 'C below the Tm, final wash solution of 6 x SSC, and final wash at 22 'C; (iii) hybridization solution of 6 x SSC and I % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 [tg/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature. 25 The detection of hybrid duplexes can be carried out by a number of methods. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Such labels refer to radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art. A label can be conjugated to either the oligonucleotide probes or the nucleic acids derived from the biological sample.

WO 2005/072050 PCT/IB2005/000433 151 Probes can be labeled according to numerous well known methods. Non- limiting examples of radioactive labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in 5 sensitivity of the method of the invention, include biotin and radio- nucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe. For example, oligonucleotides of he present invention can be labeled subsequent to synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means (e.g., photo 10 cross-linking a psoralen derivative of biotin to RNAs), followed by addition of labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent. Alternatively, when fluorescently- labeled oligonucleotide probes are used, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al. (1992), Academic Press San Diego, Calif] can be attached to the 15 oligonucleotides. Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes. 20 It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. For instance, samples may be hybridized to an irrelevant probe and treated with RNAse A prior to hybridization, to assess false hybridization. Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing 25 the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods. As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples of radioactive labels include 3 H, 4c, 32 P, and "S. 30 Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay WO 2005/072050 PCT/IB2005/000433 152 formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes. It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. 5 Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and a-nucleotides and the like. Probes of the invention can be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA. 10 NAT Assays Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example). As used herein, a "primer" defines an oligonucleotide which is capable of annealing to 15 (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions. Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit 20 particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and 25 Sambrook et al., 1989, supra). The terminology "amplification pair" (or "primer pair") refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes 30 include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based WO 2005/072050 PCT/IB2005/000433 153 amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions. In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially 5 expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of 10 differentially expressed nucleic acid sequences. The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods. Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes 15 employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning -A Laboratory Manual, 20 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.). It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected 25 based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity. The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non- limiting examples of these reactions are described in greater detail 30 below). The pair of oligonucleotides according to this aspect of the p-esent invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures WO 2005/072050 PCT/IB2005/000433 154 which differ by less than that 7 'C, preferably less than 5 0 C, more preferably less than 4 'C, most preferably less than 3 'C, ideally between 3 'C and 0 "C. Polymerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing 5 the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands 10 of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to form complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired 15 target sequence. The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be "PCR-amplified." 20 Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as "Ligase Amplification Reaction" (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two- adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is 25 added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base 30 changes: see for example Segev, PCT Publication No. W09001069 Al (1990). However, because the four oligonuc leotides used in this assay can pair to form two short ligatable WO 2005/072050 PCT/IB2005/000433 155 fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions. Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially 5 amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5' end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo-and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of 10 transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs). Q-Beta (QP) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Qffi replicase. A previously identified 15 major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to 20 detect a mutation at the junction site, but not elsewhere. A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and QD systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., > 25 55 degrees C). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies. 30 The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the WO 2005/072050 PCT/IB2005/000433 156 population with each cycle. The final yield of any such doubling system can be expressed as: (i+X)n =y, where "X" is the mean efficiency (percent copied in each cycle), "n" is the number of cycles, and "y" is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 5 100 %. If 20 cycles of PCR are performed, then the yield will be 220, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85 %, then the yield in those 20 cycles will be only 1.8520, or 220,513 copies of the starting material. In other words, a PCR running at 85 % efficiency will yield only 21 % as much final product, compared to a reaction running at 100 % efficiency. A reaction that is reduced to 50 % mean efficiency will 10 yield less than 1 % of the possible product. In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50 % mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes 15 prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products. Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA 20 (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to 25 penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling. Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also 30 the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq WO 2005/072050 PCT/IB2005/000433 157 polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3' end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. 5 This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect. A similar 3'-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the 10 drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory. The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis. 15 When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal 20 intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the "Cycling Probe Reaction" (CPR), and "Branched DNA" (bDNA). 25 Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe 30 molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates WO 2005/072050 PCT/IB2005/000433 158 at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation. Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline 5 phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased. The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, 10 Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF). The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, 15 and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing. A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning 20 the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor- intense and expensive to be practical and effective in the clinical setting. In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule 25 can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or 30 by primer extension in the presence of chain-terminating nucleotide analogs.

WO 2005/072050 PCT/IB2005/000433 159 Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct 5 sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis). Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated 10 by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the "Mismatch Chemical Cleavage" (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory. 15 RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes have 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. 20 Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites. A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly 25 clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number. Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a 30 match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based WO 2005/072050 PCT/IB2005/000433 160 on the differences in the melting temperature of short DNA fragme:ts differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip 5 oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations. With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are 10 inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest. Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor seqnce changes. One of these methods, termed "Denaturing Gradient Gel Electrophoresis" (DGGE) is 15 based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes ii their electrophoretic mobilities. The fragments to be 20 analyzed, usually PCR products, are "clamped" at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC "clamp" to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the 25 technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes. Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during 30 electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long WO 2005/072050 PCT/IB2005/000433 161 running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGE). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations. 5 A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to 10 running the gel. Single-Strand Conformation Polymoiphism (SSCP): Another common method, called "Single-Strand Conformation Polymorphism" (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence 15 electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations. The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is 20 labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions. 25 Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments 30 as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the WO 2005/072050 PCT/IB2005/000433 162 analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations). In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of 5 greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90 % of single-base substitutions within a 200 base-pair fragment, the detection drops 10 to less than 50 % for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened. According to a presently preferred embodiment of the present invention the step of 15 searching for any of the nucleic acid sequences described here, in tumor cells or in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, QP-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific 20 oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting. Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes tle candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as 25 phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station. describe the fabrication of fluidics devices and particularly microcapillary devices, in silicon and glass substrates. Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the 30 reporter groups already incorporated into the nucleic acid, which is now bound to the probes WO 2005/072050 PCT/IB2005/000433 163 attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be determined. It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or 5 pathological condition both rapidly and easily. Amino acid sequences and peptides The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one 10 or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms "polypeptide," "peptide" and "protein" include glycoproteins, as well as non-glycoproteins. Polypeptide products can be biochemically synthesized such as by employing standard 15 solid phase techniques. Such methods include but are not limited to exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry. 20 Solid phase polypeptide synthesis procedures are well known in the art and further described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984). Synthetic polypeptides can optionally be purified by preparative high performance liquid chromatography [Creighton T. (1983) Proteins, structures and molecular principles. WH 25 Freeman and Co. N.Y.], after which their composition can be confirmed via amino acid sequencing. In cases where large amounts of a polypeptide are desired, it can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516 544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511 30 514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 WO 2005/072050 PCT/IB2005/000433 164 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463. The present invention also encompasses polypeptides encoded by the polynucleotide sequences of the present invention, as well as polypeptides according to the amino acid 5 sequences described herein. The present invention also encompasses homologues of these polypeptides, such homologues can be at least 50 %, at least 55 %, at least 6 0%, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 95 % or more say 100 % homologous to the amino acid sequences set forth below, as can be determined using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters, 10 optionally and preferably including the following: filtering on (this option filters repetitive or low-complexity sequences from the query using the Seg (protein) program), scoring matrix is BLOSUM62 for proteins, word size is 3, E valuee is 10, gap costs are 11, 1 (initialization and extension), and number of alignments shown is 50. Finally, the present invention also encompasses fragments of the above described polypeptides and polypeptides having mutations, 15 such as deletions, insertions or substitutions of one or more amino acids, either naturally occurring or artificially induced, either randomly or in a targeted fashion. Homology/identity of nucleic acid sequences is preferably determined by using BlastN software of the National Center of Biotechnology Information (NCBI) using default parameters, which preferably include using the DUST filter program, and also preferably include having an E value of 10, filtering low 20 complexity sequences and a word size of 11. It will be appreciated that peptides identified according the present invention may be degradation products, synthetic peptides or recombinant peptides as well as peptidomimetics, typically, synthetic peptides and peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or 25 more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, including, but not limited to, CH2-NH, CH2-S, CH2-S=O, O=C-NH, CH2-0, CH2-CH2, S=C-NH, CH=CH or CF=CH, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further tails in this 30 respect are provided hereinunder.

WO 2005/072050 PCT/IB2005/000433 165 Peptide bonds (CO-NH-) within the peptide may be substituted, for example, by N methylated bonds (-N(CH3)-CO-), ester bonds (-C(R)H-C-0-0-C(R)-N-), ketomethylen bonds (-CO-CH2-), ac-aza bonds (-NH-N(R)-CO-), wherein R is any alkyl, e.g., methyl, carba bonds ( CH2-NH-), hydroxyethylene bonds (-CH(OH)-CH2-), thioamide bonds (-CS-NH-), olefinic 5 double bonds (-CH=CH-), retro amide bonds (-NH-CO-), peptide derivatives (-N(R)-CH2-CO-), wherein R is the "normal" side chain, naturally presented on the carbon atom. These modifications can occur at any of the bonds along the peptide chain and even at several (2-3) at the same time. Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for synthetic non 10 natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe, halogenated derivatives of Phe or o- methyl- Tyr. In addition to the above, the peptides of the present invention may also include one or more modified amino acids or one or more non-amino acid monomers (e.g. fatty acids, complex carbohydrates etc). 15 As used herein in the specification and in the claims section below the term "amino acid" or "amino acids" is understood to include the 20 naturally occurring amino acids; those amino acids often modified post-translationally in vivo, including, for example, hydroxyproline, phosphoserine and phosphothreonine; and other unusual amino acids including, but not limited to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine and ornithine. 20 Furthermore, the term "amino acid" includes both D- and I-amino acids. Table 1 non-conventional or modified amino acids which can be used with the present invention. Table 1 25 Non-conventional amino Code Non-conventional amino acid Code acid a-aminobutyric acid Abu L-N-methylalanine Nmala a-amino-a-methylbutyrate Mgabu L-N-methylarginine Nmarg aminocyclopropane- Cpro L-N-methylasparagine Nmasn WO 2005/072050 PCT/1B2005/000433 166 Carboxylate L-N-methylaspartic acid Nmasp aminoisobutyric acid Aib L-N-methylcysteine Nmcys aminonorbornyl- Norb L-N-methylglutamifle Nmgin Carboxylate L-N-methylglutamic acid Nmglu Cyclohexylalanine Chexa L-N-methylhstidine Nmhis Cyclopentylalanifle Cpen L-N-methylisolleucine Nmile D-alanine Dal L-N-methylleucie Nmleu D-arginine Darg L-N-methyllysine Nmlys D-aspartic acid Da-sp L-N-methyl methionine Nn'met D-cysteine Dcys L-N-methylnorleucine Nn-Lle D-glutamine Dgln L-N-methylnorvaline Nmnva D-glutamic acid Du L-N-methylomithine Nmorn D-histidine Dhis L-N-methylphenylaianine Nmphe D-isoleucine Dile L-N-methylproline Nmpro D-luieDleu L-N-rnethylserine Nmser D-yieDlys L-N-methylthreonine Nmtbr D-methionine Dmet L-N--methyltryptophan Nmtrp D-ornithine Domn L-N-methyltyrosine Nmtyr D-phenytalanine Dpe L-N-methylvaline Nrnval D-proline Dpro L-N-methylethylglycine Nmetg D-serine Dser L-N-methyl-t-butylglycine Nmtbug D-.threonine Dthr L-norleucine NMe D-tryptophan Dtrp L-norvaline Nva D-tyrosine Dtrx-methyl-aminolsobutyrate Maib D-valine Dval ca-methy-y-aminobutyrate Mgabu D- c-methylalanine D-5mala c.-methyleyclohexylaianine Mchexa D-c-methylarginine Dmarg a-rnetlhylcyclopentylalanine Mcpen D- cx-methylasparagine D-6masn (x-methyl-c-napthylalanine Manap D-cr-methylaspartate Dmasp c- methyleIilamine Me WO 2005/072050 PCT/1B2005/000433 167 D-c,, -methylcysteine Dmcys N-(4-amidnobutyl)glycine Nglu D-'of>-ethylglutamine Dmgln N-(2-aminoethyl)glycine Naeg D-cu-methy~Hstidline Dmhis N-(3-aminopropyl)glycine Nom D-u**methylisoleucine Dmile N- amino- a- methylbutyrate Nmaabu D-ca-methylleucine Dmleu cx-napthylalanine Anap D-c-methyllysine Dmlys N-benzylglycine Nphe D-cx-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln D-ac-methylomithine Dmorn N- (carbamylmethyl)glycine Nasn D-oa-methylphenylalariine Dmpl-e N-(2-carboxyethyl)glycine Nglu D-a-methylproline Dmpro N-(carboxymethyl)glycine Nasp D-a-methylserine Dmser N-cyclobutylglycine Ncbut D-cc-methyltbreonine Dmthr N-cycloheptylglycine Nchep D-cc-methyltryptophan Dmtrp N-cyclohexylglycine Nchex D-a-methyltyrosine Dmty N-cyclodecylglycine Ncdec D- c-methylvaline Drnval N-cyclododeclglycine Ncdod D-ca-methylalnine Dnmala N-cyclooctylglycine Ncoct D- x-methylarginine Dnmarg N-cyclopropylglycine Ncpro D- x-rethylasparagine Dnmasn N-cycloundecylglycine Ncund D-ca-methylasparatate Dnmasp N- (2,2-diphenylethyl)glycine Nbhm D-ca-methylcysteine Dnmcys N-(3,3- Nbhe diphenylpropyl)glycine D-N-methylleucine Dnrnleu N-(3-indolylyethyl) glycie Nhtrp D-N-methyllysine Dnimlys N-methyl- y-aminobutyrate Nmigabu N- Nmchexa D-N-methyimethionine Dnmmet methyloyclohexylalanine D-N-methylomithine Dnmorn N-methylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnimphe N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro N-(1-methylpropyl)glycine Nile D-N-methylserine Dnniser WO 2005/072050 PCT/1B2005/000433 168 N-(2-methylpropyl)glycine Nile D-N-methylserine Drimser N- (2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-methyltryptophan Ditrp N-(1-methylethyl)glycine Nva D-N-methyltyrosine Dnnityr N-methyla- napthylalanine Nmanap D-N-methylvaline Dnnwal N-methylpenicillamnine Nmpen y-amninobutyric acid Gabu N-(p-hycfroxyphenyl)glycine Nhtyr L-t-butylglycine Thug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillarnine Pen L-homophenylalanine Hphe L-ctc-methylalanine Mala L-c(x-methylarginine Marg L- ox-methylasparagine Masn L- ix-methylaspartate Masp L- x-methyl- t-butylglycine Mtbug L-ca-methylcysteine Mcys L- methylethylglycine Metg L- ca-methylglutamnine Mgln U- ox-methylglutamate Mglu L-ot,-methylhistidine Mhfis L-c-methylhomo Mhfphe phenylalanine L-x- methylisoleucine Mile N-(2- methylthioethyl)glycine Nmet D-N-methylglutamnine Dnmgln N-(3- Narg guanidinopropyl)glycine D-N-methylglutamnate Dnmglu N-(1 -hydroxyethyl)glycine Nthr D-N-methylhstidine Dnmhis N-(hyclroxyethyl)glycine Nser D-N-methylisoleucine Dnile N- (imidazolylethyl)glycine Nhis D-N-methylleucine Dnrnleu N-(3- indolylyethyl)glycine Nlitr D-N-methyllysine Dnmlys N-methyl- y-aminobutyrate Nmgabu N- Nmchexa D-N-methylmethionine Dnmimet methylcyclohexylalanine D-N-methylomnithine Dnmorn N-rnethylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylamninoisobutyrate Nmaib D-N-methylproline Dnmpro N- (1-methylpropyl)glycine Nile D-N-methylserine Dnrnser WO 2005/072050 PCT/1B2005/000433 169 N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmnthr D-N-methyltryptophan Dnmtrp N- (I-methylethyl)glycine Nval D-N-methyltyrosine Dnmtyr N-methyla- napthylalanine Nmanap D-N-methylvaline Dnmval N-methylpenicillamnine Nmpen y-aminobutyric acid Gabu N-(?p-hydroxyphenyl)glycine 7Nhtyr L-t-butylglycine Thug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-homophenylalanine Hphe L- cx-methylaiine Mala L- u-methylarginine Marg L- ci-methylasparagine Masn L-c-methylaspartate Masp Lu-o-methyl- t-butylglycine Mtbug L- cc-methylcysteine Mcys L- methylethylglycine Metg L-a-rethylglutamine Mgln L-cc-methylglutamate Mglu L-cx-methylhistidine Mihis L-cx- Mhphe rnethylhomophenylaianine L- cx-methylisoleucine Mie N-(2-methylthioethyl)glycine Nmet L- ox-methyIleucine Mleu L- x-methyllysine Nflys L-ctx-methylmethionine Mmet L-cx-methylnorleucine Mnle L- x-methylnorvaline Mnva L- cx-methylornithine Momn L-ca-rethylphenylalanine Mphe L- x- methyiproline Mpro L-x-methylserine mser L- cx-methyltlireonine Mthr L-oa-methylvaline Mtrp L-c-methyltyrosine Mityr L-Qx-methylleucine Mival L-N- Nmhphe Nnbhni methyihomophenylalanine N-(N-(2,2-diphenylethyl) N-(N- (3 ,3-.diphenylpropyl) carbamylmethyl-glycine Nnbhrn carbamylmethyl(I1)glycine Nnbhe 1- carboxy- 1- (2,2- diphenyl Nmbc ethylamino)cyclopropane Table 1 Cont.

WO 2005/072050 PCT/IB2005/000433 170 Since ibe peptides of the present invention are preferably utilized in diagnostics which require the peptides to be in soluble form, the peptides of the present invention preferably include one or more non-natural or natural polar amino acids, including but not limited to serine and threonine which are capable of increasing peptide solubility due to their hydroxyl-containing 5 side chain. The peptides of the present invention are preferably utilized in a linear form, although it will be appreciated that in cases where cyclicization does not severely interfere with peptide characteristics, cyclic forms of the peptide can also be utilized. The peptides of present invention can be biochemically synthesized such as by using 10 standard solid phase techniques. These methods include exclusive solid phase synthesis well known in the art, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry. 15 Synthetic peptides can be purified by preparative high performance liquid chromatography and the composition of which can be confirmed via amino acid sequencing. In cases where large amounts of the peptides of the present invention are desired, the peptides of the present invention can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) 20 Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and also as described above. 25 Antibodies "Antibody" refers to a polypeptide ligand that is preferably substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds 30 and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon and mu WO 2005/072050 PCT/IB2005/000433 171 heavy chain constant region genes, and the myriad-immunoglobulin variable region genes. Antibodies exist, e.g., as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. This includes, e.g., Fab' and F(ab)' 2 fragments. The term "antibody," as used herein, also includes antibody fragments either produced by the 5 modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies. It also includes polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. "Fc" portion of an antibody refers to that portion of an immunoglobulin heavy chain that comprises one or more heavy chain constant region domains, CHI, CH2 and CH3, but does not include the heavy chain variable 10 region. The functional fragments of antibodies, such as Fab, F(ab')2, and Fv that are capable of binding to macrophages, are described as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy 15 chain; (2) Fab', the fragment of an antibody molecule that can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together by two disulfide 20 bonds; (4) Fv, defined as a genetically engineered fragment containing the variable region of the light chain aid the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody ("SCA"), a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. 25 Methods of producing polyclonal and monoclonal antibodies as well as fragments thereof are well known in the art (See for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by reference). Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster 30 ovary cell culture or other protein expression systems) of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by WO 2005/072050 PCT/IB2005/000433 172 conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab')2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' 5 monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained therein, which patents are hereby incorporated by reference in their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies, such as separation 10 of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody. Fv fragments comprise an association of VH and VL chains. This association may be noncovalent, as described in Inbar et al. [Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. 15 Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VH and VL domains connected by an oligonucleotide. The structural gene is inserted into an expression 20 vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by [Whitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference in its entirety. 25 Another form of an antibody fragment is a peptide coding for a single complementarity determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: 106-10 (1991)]. 30 Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') or WO 2005/072050 PCT/IB2005/000433 173 other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as 5 mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in 10 which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323 15 329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)]. Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially 20 performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science, 239:1534 1536 (1988)], by substituting rodert CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been 25 substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); 30 Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal WO 2005/072050 PCT/IB2005/000433 174 Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991)]. Similarly, human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human 5 antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10,: 779 783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); 10 Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995). Preferably, the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention. As used herein, the term "epitope" refers to any antigenic determinant on an antigen to which the paratope of an antibody 15 binds. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Optionally, a unique epitope may be created in a variant due to a change in one or more 20 post-translational modifications, including but not limited to glycosylation and/or phosphorylation, as described below. Such a change may also cause a new epitope to be created, for example through removal of glycosylation at a particular site. An epitope according to the present invention may also optionally comprise part or all of a unique sequence portion of a variant according to the present invention in combination with at 25 least one other portion of the variant which is not contiguous to the unique sequence portion in the linear polypeptide itself, yet which are able to form an epitope in combination. One or more unique sequence portions may optionally combine with one or more other non-contiguous portions of the variant (including a portion which may have high homology to a portion of the known protein) to form an epitope. 30 Immunoassays WO 2005/072050 PCT/IB2005/000433 175 In another embodiment of the present invention, an immunoassay can be used to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises: providing an antibody that specifically binds to a marker; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample. 5 To prepare an antibody that specifically binds to a marker, purified protein markers can be used. Antibodies that specifically bind to a protein marker can be prepared using any suitable methods known in the art. After the antibody is provided, a marker can be detected and/or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, 10 an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained from a subject can be contacted with the antibody that specifically binds the marker. Optionally, the antibody can be fixed to a solid support to facilitate washing and 15 subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are not limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies can also be attached to a solid support. After incubating the sample with antibodies, the mixture is washed and the antibody marker complex formed can be detected. This can be accomplished by incubating the washed 20 mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture. 25 Throughout the assays, incubation and/or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations and the like. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range 30 of temperatures, such as 10 'C to 40 0

C.

WO 2005/072050 PCT/IB2005/000433 176 The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample can be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibod-marker complex with an antibody that specifically binds the marker under suitable incubation 5 conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and/or signal. Preferably used are antibodies which specifically interact with the polypeptides of the 10 present invention and not with wild type proteins or other isoforms thereof, for example. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the present invention, including but not limited to bridges, heads, tails and insertions described in greater detail below. Preferred embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled "Antibodies". 15 Radio-immunoassay (RIA): In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and radiolabelled antibody binding protein (e.g., protein A labeled with 1125) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate. 20 In an alternate version of the RIA, a labeled substrate and an unlabelled antibody binding protein are employed. A sample containing an unknown amount of substrate is added in varying amounts. The decrease in precipitated counts from the labeled substrate is proportional to the amount of substrate in the added sample. Enzyme linked inmunosorbent assay (ELISA,): This method involves fixation of a sample 25 (e.g., fixed cells or a proteinaceous solution) containing a protein substrate to a surface such as a well of a microtiter plate. A substrate specific antibody coupled to an enzyme is applied and allowed to bind to the substrate. Presence of the antibody is then detected and quantitated by a colorimetric reaction employing the enzyme coupled to the antibody. Enzymes commonly employed in this method include horseradish peroxidase and alkaline phosphatase. If well 30 calibrated and within the linear range of response, the amount of substrate present in the sample WO 2005/072050 PCT/IB2005/000433 177 is proportional to the amount of color produced. A substrate standard is generally employed to improve quantitative accuracy. Western blot: This method involves separation of a substrate from other protein by means of an acrylamide gel followed by transfer of the substrate to a membrane (e.g., nylon or PVDF). 5 Presence of the substrate is then detected by antibodies specific to the substrate, which are in turn detected by antibody binding reagents. Antibody binding reagents may be, for example, protein A, or other antibodies. Antibody binding reagents may be radiolabelled or enzyme linked as described hereinabove. Detection may be by autoradiography, colorimetric reaction or chemiluminescence. This method allows both quantitation of an amount of substrate and 10 determination of its identity by a relative position on the membrane which is indicative of a migration distance in the acrylamide gel during electrophoresis. Inimunohistochemical analysis: This method involves detection of a substrate in situ in fixed cells by substrate specific antibodies. The substrate specific antibodies may be enzyme linked or linked to fluorophores. Detection is by microscopy and subjective evaluation. If 15 enzyme linked antibodies are employed, a colorimetric reaction may be required. Fluorescence activated cell sorting (FACS): This method involves detection of a substrate in situ in cells by substrate specific antibodies. The substrate specific antibodies are linked to fluorophores. Detection is by means of a cell sorting machine which reads the wavelength of light emitted from each cell as it passes through a light beam. This method may 20 employ two or more antibodies simultaneously. Radio-imaging Methods These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non 25 invasive, and can be used to detect and/or measure a wide variety of tissue events and/or functions, such as detecting cancerous cells for example. Unlike PET, SPECT can optionally be used with two labels simultaneously. SPECT has some other advantages as well, for example with regard to cost and the types of labels that can be used. For example, US Patent No. 6,696,686 describes the use of SPECT for detection of breast cancer, and is hereby incorporated 30 by reference as if fully set forth herein.

WO 2005/072050 PCT/IB2005/000433 178 Display Libraries According to still another aspect of the present invention there is provided a display library comprising a plurality of display chicles (such as phages, viruses or bacteria) each displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15, 12-17, 15-20, 15-30 or 20 5 50 consecutive amino acids derived from the polypeptide sequences of the present invention. Methods of constructing such display libraries are well known in the art. Such methods are described in, for example, Young AC, et al., "The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes" J Mol 10 Biol 1997 Dec 12;274(4):622-34; Giebel LB et al. "Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities" Biochemistry 1995 Nov 28;34(47):15430-5; Davies EL et al., "Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes" J Immunol Methods 1995 Oct 12;186(1):125-35; Jones C RT al. "Current trends in molecular recognition and bioseparation" J 15 Chromatogr A 1995 Jul 14;707(l):3-22; Deng SJ et al. "Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries" Proc Natl Acad Sci U S A 1995 May 23;92(11):4992-6; and Deng SJ et al. "Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display" J Biol Chem 1994 Apr 1;269(13):9533-8, which are incorporated herein by reference. 20 The following sections relate to Candidate Marker Examples (first section) and to Experimental Data for these Marker Examples (second section). CANDIDATE MARKER EXAMPLES SECTION 25 This Section relates to Examples of sequences according to the present invention, including illustrative methods of selection thereof. Description of the methodology undertaken to uncover the biomolecular sequences of the present invention Human ESTs and cDNAs were obtained from GenBank versions 136 (June 15, 2003 30 ftp.ncbi.nih.gov/genbank/release.notes/gb136.release.notes); NCBI geno me assembly of April 2003; RefSeq sequences from June 2003; Genbank version 139 (December 2003); Human WO 2005/072050 PCT/IB2005/000433 179 Genome from NCBI (Build 34) (from Oct 2003); RefSeq sequences from December 2003; and from LifeSeq library of Incyte Corp (Wilmington, DE, USA; ESTs only). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section and the human mRNA sequences from the primate (GBPRI) section were used; also the human nucleotide 5 RefSeq mRNA sequences were used (see for example www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.htrml and for a reference to the EST section, see www.ncbi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST database in GenBank, may be found in Boguski et al, Nat Genet. 1993 Aug;4(4):332-3; all of which are hereby incorporated by reference as if fully set forth herein). 10 Novel splice variants were predicted using the LEADS clustering and assembly system as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); US patent No: 6,625,545; and U.S. Pat. Apple. No. 10/426,002, published as US20040101876 on May 27 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from 15 repeats, vectors and immunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into "clusters" that represent genes or partial genes. These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich pool of annotations, sequence information (particularly of 20 spliced sequences), chromosomal information, alignments, and additional information such as SNPs, gene ontology terms, expression profiles, functional analyses, detailed domain structures, known and predicted proteins and detailed homology reports. A brief explanation is provided with regard to the method of selecting the candidates. However, it should noted that this explanation is provided for descriptive purposes only, and is 25 not intended to be limiting in any way. The potential markers were identified by a computational process that was designed to find genes and/or their splice variants that are over-expressed in tumor tissues, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to a manual classification process, were used to assist in locating genes and/or splice variants thereof that are over-expressed in 30 cancerous tissues. The detailed description of the selection method is presented in Example 1 WO 2005/072050 PCT/IB2005/000433 180 below. The cancer biomarkers selection engine and the following wet validation stages are schematically summarized in Figure 1. EXAMPLE 1 5 Identification of differentially expressed gene products - Algorithm In order to distinguish between differentially expressed gene products and constitutively expressed genes (i.e., house keeping genes ) an algorithm based on an analysis of frequencies was configured. A specific algorithm for identification of transcripts over expressed in cancer is described hereinbelow. 10 Dry analysis Library annotation - EST libraries are manually classified according to: (i) Tissue origin (ii) Biological source - Examples of frequently used biological sources for construction of EST libraries include cancer cell- lines; normal tissues; 15 cancer tissues; fetal tissues; and others such as normal cell lines and pools of normal cell-lines, cancer cell-lines and combinations thereof. A specific description of abbreviations used below with regard to these tissues/cell lines etc is given above. 20 (iii) Protocol of library construction - various methods are known in the art for library construction including normalized library construction; non-normalized library construction; subtracted libraries; ORESTES and others. It will be appreciated that at times the protocol of library construction is not indicated. 25 The following rules were followed: EST libraries originating from identical biological samples are considered as a single library. EST libraries which included above-average levels of contamination, such as DNA contamination for example, were eliminated. The presence of such contamination was determined 30 as follows. For each library, the number of unspliced ESTs that are not fully contained within other spliced sequences was counted. If the percentage of such sequences (as compared to all WO 2005/072050 PCT/IB2005/000433 181 other sequences) was at least 4 standard deviations above the average for all libraries being analyzed, this library was tagged as being contaminated and was eliminated from further consideration in the below analysis (see also Sorek, R. & Safer, H.M. A novel algorithm for computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 5 (2003)for further details). Clusters (genes) having at least five sequences including at least two sequences from the tissue of interest were analyzed. Splice variants were identified by using the LEADS software package as described above. 10 EXAMPLE 2 Identification of genes over expressed in cancer. Two different scoring algorithms were developed. Libraries score -candidate sequences which are supported by a number of cancer libraries, are more likely to serve as specific and effective diagnostic markers. 15 The basic algorithm - for each cluster the number of cancer and normal libraries contributing sequences to the cluster was counted. Fisher exact test was used to check if cancer libraries are significantly over-represented in the cluster as compared to the total number of cancer and normal libraries. Library counting: Small libraries (e.g., less than 1000 sequences) were excluded from 20 consideration unless they participate in the cluster. For this reason, the total number of libraries is actually adjusted for each cluster. Clones no. score - Generally, when the number of ESTs is much higher in the cancer libraries relative to the normal libraries it might indicate actual over-expression. The algorithm 25 Clone counting: For counting EST clones each library protocol class was given a weight based on our belief of how much the protocol reflects actual expression levels: (i) non-normalized : (ii) normalized : 0.2 (iii) all other classes : 0.1 30 Clones number score - The total weighted mmber of EST clones from cancer libraries was compared to the EST clones from normal libraries. To avoid cases where one library WO 2005/072050 PCT/IB2005/000433 182 contributes to the majority of the score, the contribution of the library that gives most clones for a given cluster was limited to 2 clones. The score was computed as c+1 5 C n+1 N where: c - weighted number of "cancer" clones in the cluster. C- weighted number of clones in all "cancer" libraries. 10 n - weighted number of "normal" clones in the cluster. N- weighted number of clones in all "normal" libraries. Clones number score significance - Fisher exact test was used to check if EST clones from cancer libraries are significantly over-represented in the cluster as compared to the total number of EST clones from cancer and normal libraries. 15 Two search approaches were used to find either general cancer-specific candidates or tumor specific candidates. 0 Libraries/sequences originating from tumor tissues are counted as well as libraries originating from cancer cell-lines ("normal" cell-lines were ignored). 20 e Only libraries/sequences originating from tumor tissues are counted EXAMPLE 3 Identification of tissue specific genes For detection of tissue specific clusters, tissue libraries/sequences were compared to the 25 total number of libraries/sequences in cluster. Similar statistical tools to those described in above were employed to identify tissue specific genes. Tissue abbreviations are the same as for cancerous tissues, but are indicated with the header "normal tissue". The algorithm - for each tested tissue T and for each tested cluster the following were examined: WO 2005/072050 PCT/IB2005/000433 183 1. Each cluster includes at least 2 libraries from the tissue T. At least 3 clones (weighed - as described above) from tissue T in the cluster; and 2. Clones from the tissue T are at least 40 % from all the clones participating in the tested cluster 5 Fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant. EXAMPLE 4 Identification of splice variants over expressed in cancer of clusters which are not over 10 expressed in cancer Cancer-specific splice variants containing a unique region were identified. Identification of unique sequence regions in splice variants A Region is defined as a group of adjacent exons that always appear or do not appear together in each splice variant. 15 A "segment" (sometimes referred also as "seg" or "node") is defined as the shortest contiguous transcribed region without known splicing inside. Only reliable ESTs were considered for region and segment analysis. An EST was defined as unreliable if: (i) Unspliced; 20 (ii) Not covered by RNA; (iii) Not covered by spliced ESTs; and (iv) Alignment to the genome ends in proximity of long poly-A stretch or starts in proximity of long poly-T stretch. Only reliable regions were selected for further scoring. Unique sequence regions were 25 considered reliable if: (i) Aligned to the genome; and (ii) Regions supported by more than 2 ESTs. The algorithm Each unique sequence region divides the set of transcripts into 2 groups: 30 (i) Transcripts containing this region (group TA). (ii) Transcripts not containing this region (group TB).

WO 2005/072050 PCT/IB2005/000433 184 The set of EST clones of every cluster is divided into 3 groups: (i) Supporting (originating from) transcripts of group TA (Si). (ii) Supporting transcripts of group TB (S2). (iii) Supporting transcripts from both groups (S3). 5 Library and clones number scores described above were given to SI group. Fisher Exact Test P-values were used to check if: S1 is significantly enriched by cancer EST clones compared to S2; and Si is significantly enriched by cancer EST clones compared to cluster background (SI+S2+S3). 10 Identification of unique sequence regions and division of the group of transcripts accordingly is illustrated in Figure 2. Each of these unique sequence regions corresponds to a segment, also termed herein a "node". Region 1: common to all transcripts, thus it is preferably not considered for determining 15 differential expression between variants; Region 2: specific to Transcript 1; Region 3: specific to Transcripts 2+3; Region 4: specific to Transcript 3; Region 5: specific to Transcripts 1 and 2; Region 6: specific to Transcript 1. 20 EXAMPLE 5 Identification of cancer specific splice variants of genes over expressed in cancer A search for EST supported (no mRNA) regions for genes of: (i) known cancer markers (ii) Genes shown to be over-expressed in cancer in published micro-array experiments. 25 Reliable EST supported-regions were defined as supported by minimum of one of the following: (i) 3 spliced ESTs; or (ii) 2 spliced ESTs from 2 libraries; (iii) 10 unspliced ESTs from 2 libraries, or 30 (iv) 3 libraries.

WO 2005/072050 PCT/IB2005/000433 185 Actual Marker Examples The following examples relate to specific actual marker examples. EXPERIMENTAL EXAMPLES SECTION 5 This Section relates to Examples describing experiments involving these sequences, and illustrative, non- limiting examples of methods, assays and uses thereof. The materials and experimental procedures are explained first, as all experiments used them as a basis for the work that was performed. 10 The markers of the present invention were tested with regard to their expression in various cancerous and non-cancerous tissue samples. A description of the samples used in the panel is provided in Table 1 below. A description of the samples used in the normal tissue panel is provided in Table 2 below. Tests were then performed as described in the "Materials and Experimental Procedures" section below. 15 Table 1: Tissue samples in testing panel sample sex/ rename Lot no source pathology grade age TNM stage Invasive 1 Lobular 52-B-1LC G1 A605360 Biochain Carcinoma F/60 51-B-IDC G1 A605361 Biochain IDC 1 F/79 T2NOM stage 6-A-IDC G1 7238T ABS IDC 1 F/60 0 2A T1NOM 7-A-IDC G2 7263T ABS IDC 2 F/43 0 stage 1 T2NOM stage 12-A-IDC G2 1432T ABS IDC 2 F/46 0 2A 13-A-IDC G2 A0133T ABS IDC 2 F/63 T2N1a WO 2005/072050 PCT/IB2005/000433 186 Mx T2N2M 14-A-IDCG2 A0135T ABS IDC 2 F/37 x F3N1M stage 15-A-IDC G2 7259T ABS IDC 2 F159 0 3A T3N1M 16-A-IDC G2 4904020032T ABS IDC 2 NA x T3N1M 17-A-IDC G2 4904020036T ABS IDC 2-3 NA x 43-B-IDC G2 A609183 Biochain IDC 2 F/40 44-B-IDC G2 A609198 Biochain IDC 2 F/77 45-B-IDC G2 A609181 Biochain IDC 2 F/58 48-B-IDC G2 A609222 Biochain IDC 2 F/44 49-B-IDC G2 A609223 Biochain IDC 2 F154 50-B-IDC G2 A609224 Biochain IDC 2 F/69 53-B-IDC G2 A605151 Biochain IDC 2 F/44 54-B-IDC G2 A605353 Biochain IDC 2 F/41 55-B-IDC G2 A609179 Biochain IDC 2 F/42 61-B-IDC G2 A610029 Biochain IDC 2 F/46 62-B-IDC G2 A609194 Biochain IDC 2 F/51 47-B-IDC G2 A609221 Biochain IDC 2 46-B-Carci G2 A609177 Biochain Carcinoma 2 F/48 T2NOM stage 26-A-IDC G3 7249T ABS IDC 3 F/60 0 2A T2NOM 27-A-IDC G3 4907020072T ABS IDC 3 NA x TlcNO 42-A-IDC G3 6005020031T ABS IDC 3 NA Mx 31-CG-IDC CG-154 Ichilov IDC NA 32-A-Muc 7116T ABS Mucinous F/54 T2NOM stage WO 2005/072050 PCT/IB2005/000433 187 Carci carcinoma 0 2A Normal matched 35-A-N M6 7238N ABS to 6T F/60 Normal matched 36-A-N M7 7263N ABS to 7T F/43 Normal matched 39-A-N M15 7259N ABS to 15T F/59 Normal matched 40-A-N M12 1432N ABS to 12T F/46 Normal matched 41-A-N M26 7249N ABS to 26T F/60 Normal 56-B-N A609235 Biochain PM F/59 Normal 57-B-N A609233 Biochain PM F/34 Normal 58-B-N A609232 Biochain PM F/65 Normal 59-B-N A607155 Biochain PM F/35 Normal 60-B-N A609234 Biochain PM F/36 63-Am-N 26486 Ambion Normal PS F/43 Normal 64-Am-N 23036 Ambion PM F/57 65-Am-N 31410 Ambion Normal F/63 WO 2005/072050 PCT/IB2005/000433 188 PM Normal 66-Am-N 36678 Ambion PM F/45 073P0106020E Normal 67-Am-N 6A Ambion PM F/64 Table 2: Tissue samples in normal panel: Lot no. Source Tissue Pathology Sex/Age 1-Am-Colon (C71) 071P1OB Ambion Colon PM F/43 2-B-Colon (C69) A411078 Biochain Colon PM-Pool of 10 M&F 3-Cl-Colon (C70) 1110101 Clontech Colon PM-Pool of 3 M&F 4-Am-Small Intestine 091P0201A Ambion Small Intestine PM M/75 5-B-Small Intestine A501158 Biochain Small Intestine PM M/63 6-B-Rectum A605138 Biochain Rectum PM M/25 7-B-Rectum A610297 Biochain Rectum PM M/24 8-B-Rectum A610298 Biochain Rectum PM M/27 9-Am-Stomach 11OP04A Ambion Stomach PM M/16 10-B-Stomach A501159 Biochain Stomach PM M/24 11-B-Esophagus A603814 Biochain Esophagus PM M/26 12-B-Esophagus A603813 Biochain Esophagus PM M/41 13-Am-Pancreas 071P25C Ambion Pancreas PM M/25 14-CG-Pancreas CG-255-2 Ichilov Pancreas PM M/75 15-B-Lung A409363 Biochain Lung PM F/26 16-Am-Lung (L93) 111P0103A Ambion Lung PM F/61 17-B-Lung (L92) A503204 Biochain Lung PM M/28 18-Am-Ovary (047) 061P43A Ambion Ovary PM F/16 19-B-Ovary (048) A504087 Biochain Ovary PM F/51 20-B-Ovary (046) A504086 Biochain Ovary PM F/41 21-Am-Cervix 101P0101A Ambion Cervix PM F/40 WO 2005/072050 PCT/IB2005/000433 189 22-B-Cervix A408211 Biochain Cervix PM 23-B-Cervix A504089 Biochain Cervix PM-Pool of 5 M&F 24-B-Uterus A41 1074 Biochain Uterus PM-Pool of 10 M&F 25-B-Uterus A409248 Biochain Uterus PM F/43 26-B-Uterus A504090 Biochain Uterus PM-Pool of 5 M&F 27-B-Bladder A501157 Biochain Bladder PM M/29 28-Am-Bladder 071P02C Ambion Bladder PM M/20 29-B-Bladder A504088 Biochain Bladder PM-Pool of 5 M&F 30-Am-Placenta 021P33A Ambion Placenta PB F/33 31-B-Placenta A410165 Biochain Placenta PB Ff26 32-B-Placenta A41 1073 Biochain Placenta PB-Pool of 5 M&F 33-B-Breast (B59) A607155 Biochain Breast PM Ff36 34-Am-Breast (B63) 26486 Ambion Breast PM F/43 35-Am-Breast (B64) 23036 Ambion Breast PM F/57 36-Cl-Prostate (P53) 1070317 Clontech Prostate PB-Pool of 47 M&F 37-Am-Prostate (P42) 061P04A mbion Prostate PM M/47 38-Am-Prostate (P59) 25955 Ambion Prostate PM M/62 39-Am-Testis 111PO104A Ambion Testis PM M/25 40-B-Testis A411147 Biochain Testis PM M/74 41-Cl-Testis 1110320 Clontech estisPB-Pool of 45 M&F 42-CG-Adrenal CG-184-10 Ichilov Adrenal PM Ff81 43-B-Adrenal A610374 Biochain Adrenal PM Ff83 44-B-Heart A411077 Biochain Heart PB-Pool of 5 M&F 45-CG-Heart CG-255-9 Ichilov Heart PM M/75 46-CG-Heart CG-227-1 lchilov Heart PM F/36 47-Am-Liver 81PO101A Ambion Liver PM M/64 48-CG-Liver CG-93-3 Ichilov Liver PM F/19 49-CG-Liver CG-124-4 Ichilov Liver PM Ff34 50-Cl-BM 1110932 Clontech Bone Marrow PM-Pool of 8 M&F -CGEPN-Blood WMPoC#5ofGEN Blood

M

WO 2005/072050 PCT/IB2005/000433 190 52-CGEN-Blood WBC#4 CGEN Blood M 53-CGEN-Blood WBC#3 CGEN Blood M 54-CG-Spleen CG-267 lchilov Spleen PM F/25 55-CG-Spleen 11lP0106BAmbion Spleen PM M/25 56-CG-Spleen A409246 Biochain Spleen PM F/12 56-CG-Thymus CG-98-7 Ichilov Thymus PM F/28 58-Am-Thymus 1OPOOA Ambion Thymus PM M/14 59-B-Thymus A409278 Biochain Thymus PM M/28 60-B-Thyroid A610287 Biochain Thyroid PM M/27 61-B-Thyroid A610286 Biochain Thyroid PM M/24 62-CG-Thyroid CG-119-2 lchilov Thyroid PM F/66 63-Cl-Salivary Gland 1070319 Clontech Salivary Gland PM-Pool of 24 M&F 64-Am-Kidney IlIPOlOIB Ambion Kidney PM-Pool of 14 M&F 65-Cl-Kidney 1110970 Clontech Kidney PM-Pool of 14 M&F 66-B-Kidney A411080 Biochain Kidney PM-Pool of 5 M&F 67-CG-Cerebellum CG-183-5 Ichilov Cerebellum PM M/74 68-CG-Cerebellum CG-212-5 Ichilov Cerebellum PM M/54 69-B-Brain A411322 Biochain Brain PM M/28 70-Cl-Brain 1120022 Clontech Brain PM-Pool of 2 M&F 71-B-Brain A411079 Biochain Brain PM-Pool of 2 M&F 72-CG-Brain CG-151-1 lchilov Brain PM F/86 73-Am-Skeletal Muscle 1O1PO13A Ambion Skeletal Muscle PM F/28 74-Cl-Skeletal Muscle 1061038 Clontech Skeletal Muscle PM-Pool of 2 M&F Materials and Experimental Procedures RNA preparation - RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, 5 www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, TX 78744 USA, http://www.ambion.com). Alternatively, RNA was generated from tissue samples using WO 2005/072050 PCT/IB2005/000433 191 TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen). RT PCR - Purified RNA (1 pg) was mixed with 150 ng Random Hexamer primers 5 (Invitrogen) and 500 ptM dNTP in a total volume of 15.6 1l. The mixture was incubated for 5 min at 65 'C and then quickly chilled on ice. Thereafter, 5 pl of 5X SuperscriptII first strand buffer (Invitrogen), 2.4p 0. iM DTT and 40 units RNasin (Promega) were added, and the mixture was incubated for 10 min at 25 'C, followed by further incubation at 42 'C for 2 min. Then, 1 pl (200units) of Superscriptll (Invitrogen) was added and the reaction (final volume of 10 25p1) was incubated for 50 min at 42 'C and then inactivated at 70 *C for 15min. The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=S). Real-Time RT-PCR analysis- cDNA (5ptl), prepared as described above, was used as a template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The amplification was 15 effected as follows: 50 "C for 2 min, 95 'C for 10 min, and then 40 cycles of 95 *C for 15sec, followed by 60 *C for 1 min. Detection was performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence was registered and was used to calculate the relative trarscript quantity in the RT reactions. The relative quantity was calculated using the equation Q=efficiencyA-C. The efficiency of the PCR 20 reaction was calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities were normalized to the geometric mean of the relative quantities of several housekeeping (HSKP) genes. Schematic summary of quantitative real-time PCR analysis is presented in Figure 3. As shown, the x-axis shows the cycle number. The CT 25 Threshold Cycle point, which is the cycle that the amplification curve crosses the fluorescence threshold that was set in the experiment. This point is a calculated cycle number in which PCR product signal is above the background level (passive dye ROX) and still in the Geometric/Exponential phase (as shown, once the level of fluorescence crosses the measurement threshold, it has a geometrically increasing phase, during which measurements are 30 most accurate, followed by a linear phase and a plateau phase; for quantitative measurements, WO 2005/072050 PCT/IB2005/000433 192 the latter two phases do not provide accurate measurements). The y-axis shows the normalized reporter fluorescence. It should be noted that this type of analysis provides relative quantification. 5 The sequences of the housekeeping genes measured in all the examples on breast cancer panel were as follows: G6PD (GenBank Accession No. NM_000402) G6PD Forward primer: gaggccgtcaccaagaacat G6PD Reverse primer: ggacagccggtcagagctc 10 G6PD-amplicon: gaggccgtcaccaagaacattcacgagtcctgcatgagccagataggctggaaccgcatcatcgtggagaagcccttcgggagggacct gcagagctctgaccggctgtcc SDHA (GenBank Accession No. NM_004168) 15 SDHA Forward primer: TGGGAACAAGAGGGCATCTG SDHA Reverse primer: CCACCACTGCATCAAATTCATG SDHA-amplicon: TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG 20 PBGD (GenBank Accession No. BC019323), PBGD Forward primer: TGAGAGTGATTCGCGTGGG PBGD Reverse primer: CCAGGGTACGAGGCTTTCAAT PBGD-amplicon: 25 TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGAC AGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG HPRT1 (GenBank Accession No. NM_000 194), HPRT1 Forward primer: TGACACTGGCAAAACAATGCA 30 HPRT1 Reverse primer: GGTCCTTTTCACCAGCAAGCT WO 2005/072050 PCT/IB2005/000433 193 HPRTI-amplicon: TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCCAA AGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC 5 The sequences of the housekeeping genes measured in all the examples on normal tissue samples panel were as follows: RPL19 (GenBank Accession No. NM_000981), 10 RPL19 Forward primer: TGGCAAGAAGAAGGTCTGGTTAG RPL19 Reverse primer: TGATCAGCCCATCTTTGATGAG RPL 19 -amplicon: TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA 15 TATA box (GenBank Accession No. NM_003194), TATA box Forward primer: CGGTTTGCTGCGGTAATCAT TATA box Reverse primer: TTTCTTGCTGCCAGTCTGGAC TATA box -amplicon: CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT 20 CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG GCAGCAAGAAA UBC (GenBank Accession No. BC000449) UBC Forward primer: ATTTGGGTCGCGGTTCTTG JBC Reverse primer: TGCCTTGACATTCTCGATGGT 25 UBC -amplicon: ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA SDHA (GenBank Accession No. NM_004168) 30 SDHA Forward primer: TGGGAACAAGAGGGCATCTG SDHA Reverse primer: CCACCACTGCATCAAATTCATG WO 2005/072050 PCT/IB2005/000433 194 SDHA-amplicon: TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG 5 Oligonucleotide-based micro-array experiment protocol Microarray fabrication Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII 600 robot from BioRobotics Limited (Cambridge, UK). 50-mer oligonucleotides target sequences 10 were designed by Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et al, "Optical technologies and informatics", Proceedings of SPIE. Vol 4266, pp. 86-95 (2001). The designed oligonucleotides were synthesized and purified by desalting with the Sigma-Genosys system (The Woodlands, TX, US) and all of the oligonucleotides were joined to a C6 amino- modified linker at the 5' end, or being attached directly to CodeLink slides (Cat #25-6700-01. Amersham 15 Bioscience, Piscataway, NJ, US). The 50-mer oligonucleotides, forming the target sequences, were first suspended in Ultra-pure DDW (Cat # 01-866-lA Kibbutz Beit-Haemek, Israel) to a concentration of 50pM. Before printing the slides, the oligonucleotides were resuspended in 300mM sodium phosphate (pH 8.5) to final concentration of 150mM and printed at 35-40% relative humidity at 21'C. 20 Each slide contained a total of 9792 features in 32 subarrays. Of these features, 4224 features were sequences of interest according to the present invention and negative controls that were printed in duplicate. An additional 288 features (96 target sequences printed in triplicate) contained housekeeping genes from Human Evaluation Library2, Compugen Ltd, Israel. Another 384 features are E.coli spikes 1-6, which are oligos to E-Coli genes which are 25 commercially available in the Array Control product (Array control- sense oligo spots, Ambion Inc. Austin, TX. Cat #178 1, Lot #1 12K06). Post-coupling processing of printed slides After the spotting of the oligonucleotides to the glass (CodeLink) slides, the slides were 30 incubated for 24 hours in a sealed saturated NaCl humidification chamber (relative humidity 70 75%).

WO 2005/072050 PCT/IB2005/000433 195 Slides were treated for blocking of the residual reactive groups by incubating them in blocking solution at 50'C for 15 minutes (10ml/slide of buffer containing 0.1M Tris, 50mM ethanolamine, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed with wash solution (1Oml/slide. 4X SSC, 0.1% 5 SDS)) at 50'C for 30 minutes on the shaker. The slides were then rinsed twice with Ultra-pure DDW, followed by drying by centrifugation for 3 minutes at 800 rpm. Next, in order to assist in automatic operation of the hybridization protocol, the slides were treated with Ventana Discovery hybridization station barcode adhesives. The printed slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device and were 10 incubated for 10 minutes in 50ml of 3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess fluid was dried and slides were then incubated for three hours in 20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding CA). The following protocol was then followed with the Genisphere 900-RP (random primer), 15 with mini elute columns on the Ventana Discovery HybStationTM, to perform the microarray experiments. Briefly, the protocol was performed as described with regard to the instructions and information provided with the device itself. The protocol included cDNA synthesis and labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems. Sunnyvale, CA.) PicoFlour, which is used with the OliGreen ssDNA Quantitation reagent and 20 kit. Hybridization was performed with the Ventana Hybridization device, according to the provided protocols (Discovery Hybridization Station Tuscon AZ). The slides were then scanned with GenePix 4000B dual laser scanner from Axon 25 Instruments Inc, and analyzed by GenePix Pro 5.0 software. Schematic summary of the oligonucleotide based microarray fabrication and the experimental flow is presented in Figures 4 and 5. Briefly, as shown in Figure 4, DNA oligonucleotides at 25uM were deposited (printed) onto Amersham 'CodeLink' glass slides generating a well defined 'spot'. These slides are 30 covered with a long-chain, hydrophilic polymer chemistry that creates an active 3-D surface that covalently binds the DNA oligonucleotides 5'-end via the WO 2005/072050 PCT/IB2005/000433 196 C6-amine modifb.ation. This binding ensures that the full length of the DNA oligonucleotides is available for hybridization to the cDNA and also allows lower background, high sensitivity and reproducibility. Figure 5 shows a schematic method for performing the microarray experiments. It 5 should be noted that stages on the left-hand or right-hand side may optionally be performed in any order, including in parallel, until stage 4 (hybridization). Briefly, on the left-hand side, the target oligonucleotides are being spotted on a glass microscope slide (although optionally other materials could be used) to form a spotted slide (stage 1). On the right hand side, control sample RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled 10 probes. It should be noted that the control and cancer samples come from corresponding tissues (for example, normal prostate tissue and cancerous prostate tissue). Furthermore, the tissue from which the RNA was taken is indicated below in the specific examples of data for particular clusters, with regard to overexpression of an oligonucleotide from a "chip" (microarray), as for example "prostate" for chips in which prostate cancerous tissue and normal tissue were tested as 15 described above. In stage 3, the probes are mixed. In stage 4, hybridization is performed to form a processed slide. In stage 5, the slide is washed and scanned to form an image file, followed by data analysis in stage 6. DESCRIPTION FOR CLUSTER T10888 20 Cluster T10888 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No T10888_PEA_1_TI I T10888_PEA _1 T4 2 TI0888_PEA-1-T5 3 T10888_PEA_1_T6 4 25 Table 2 - Segments of interest WO 2005/072050 PCT/IB2005/000433 197 Segment Name Sequence ID No. T10888_PEA_1_node 11 5 T10888_PEA_1_node_12 6 T10888_PEA-1 node_17 7 T10888_PEA_1_node_4 8 T10888_PEA-1-node 6 9 T10888_PEA_1-node_7 10 T10888_PEA_1_node_9 11 T10888_PEA_1_node 15 12 Table 3 - Proteins of interest Protein Name Sequence ID No. T10888_PEA_1_P2 14 T10888_PEA_1_P4 15 T10888_PEA-lP5 16 T10888_PEA_1_P6 17 These sequences are variants of the known protein Carcinoembryonic antigen-related cell 5 adhesion molecule 6 precursor (SwissProt accession identifier CEA6-HUMAN; known also according to the synonyms Normal cross-reacting antigen; Nonspecific crossreacting antigen; CD66c antigen), SEQ ID NO: 13, referred to herein as the previously known protein. The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor is given at the end of the application, as "Carcinoembryonic antigen-related cell 10 adhesion molecule 6 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 138 F->L WO 2005/072050 PCT/IB2005/000433 198 239 V-> G Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor localization is believed to be Attached to the membrane by a GPI-anchor. The previously known protein also has the following indication(s) and/or potential 5 therapeutic use(s): Cancer. It has been investigated for clinical/therapeutic use in humans, for example as a tart for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. 10 The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Imaging agent; Anticancer; Immunostimulant; Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody. The following GO Annotation(s) apply to the previously known protein. The following 15 annotation(s) were found: signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and integral plasma membrane protein, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.chl/sprot/>; or Locuslink, available 20 from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster T10888 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of 25 the table and the numbers on the y-axis of Figure 6 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 30 Figure 6 and Table 5. This cluster is overexpressed (at least at a minimum level) in the WO 2005/072050 PCT/IB2005/000433 199 following pathological conditions: colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma. Table 5 - Normal tissue distribution Name of Tissue Number Bladder 0 Colon 107 Epithelial 52 General 22 head and neck 40 Lung 237 Breast 0 pancreas 32 Prostate 12 Stomach 0 5 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 'P2 SPI R3 SP' R4 Bladder 5.4e-01 3.4e-01 5.6e-01 1.8 4.6e-01 1.9 Colon 1.2e-01 1.7e-01 2.8e-05 3.7 7.9e-04 2.8 epithelial 3.3e-02 2.le-01 2.8e-20 2.8 4.8e-10 1.9 General 3.3e-05 2.2e-03 1.9e-44 4.9 4.6e-27 3.3 head and neck 4.6e-01 4.3e-01 1 0.8 7.5e-01 1.0 Lung 7.6e-01 8.2e-01 8.9e-01 0.6 1 0.3 Breast 3.7e-02 4.le-02 1.5e-01 3.3 3.le-01 2.4 pancreas 2.6e-01 2.4e-01 8.6e-23 2.8 1.5e-19 4.5 Prostate 9.le-01 9.3e-01 4.le-02 1.2 1.Oe-01 1.0 Stomach 4.5e-02 5.6e-02 5.le-04 4.1 4.7e-04 6.3 WO 2005/072050 PCT/IB2005/000433 200 As noted above, cluster T10888 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor. A description of each variant protein according to the present invention is now provided. 5 Variant protein T10888_PEAl-P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888-PEAI_Ti. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more 10 alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T10888_PEAlP2 and CEA6_HUMAN: 15 1.An isolated chimeric polypeptide encoding for T10888-PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL 20 WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1 - 319 of CEA6-HUMAN, which also corresponds to amino acids 1 - 319 of T10888_PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 25 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP corresponding to amino acids 320 - 324 of T10888_PEA_1_P2, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP in T10888_PEA_1_P2.

WO 2005/072050 PCT/IB2005/000433 201 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA_1_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA-lP2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP position(s):on amino acid Alternative amino acid(s) Previously known SNP? sequence 13 V-> No 232 N -> D No 324 P -> No 63 1-> No 92 G No 15 Variant protein T10888_PEA_1P2 is encoded by the following transcript(s): T10888_PEA_1_TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_1-TI is shown in bold; this coding portion starts at position 151 and ends at position 1122. The transcript also has the following SNPs as listed in 20 Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA__P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072050 PCT/IB2005/000433 2 0 2 Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C ->T No 120 A ->T No 1062 A ->G Yes 1120 C-> No 1297 G->T Yes 1501 A->G Yes 1824 G->A No 2036 A -> C No 2036 A->G No 2095 A->C No 2242 A -> C No 2245 A -> C No 189 C -> No 2250 A->T Yes 2339 C -> A Yes 276 G->A Yes 338 T-> No 424 G -> No 546 A->G No 702 C -> T No 844 A -> G No 930 C -> T Yes Variant protein T10888_PEA_1_P4 according to the present invention has an amino acid 5 sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA_1_T4. An alignment is given to the known protein (Carcinoembryonic antigen- WO 2005/072050 PCT/IB2005/000433 203 related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A briefdescription of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between T10888_PEA_1_P4 and CEA6_HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEAlP4, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP 10 QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1 - 234 of CEA6_HUMAN, which also corresponds to amino acids 1 - 234 of T10888_PEAlP4, and a second amino acid sequence being at least 70%, 15 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of T10888-PEA_1-P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL in T10888_PEA_1_P4. 25 Comparison report between T10888_PEA_1_P4 and Q13774 (SEQ [D NO:829): 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLT[ESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG 30 FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WO 2005/072050 PCT/IB2005/000433 204 WWVNGQSLPVSPRLQLSNGNMTLTLLSVYA<RNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids I - 234 of Q13774, which also corresponds to amino acids 1 - 234 of T10888_PEA_P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 5 homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of T10888_PEA_1 P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL in T10888_PEA_1_P4. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA-1_P4 also has the following non-silent SNPs (Single 20 Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1-P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 25 Table 9 - Amino acid mutations SNP position(s) on amino acid Alternative arnino acid(s) Previously known SNP? sequence 13 V-> No 232 N ->D No 63 I-> No WO 2005/072050 PCT/IB2005/000433 205 92 G-> No Variant protein T10888_PEA_1_P4 is encoded by the following transcript(s): T10888_PEA-lT4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_1_T4 is shown in bold; this coding portion starts at 5 position 151 and ends at position 918. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888-PEAlP4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 10 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C ->T No 120 A ->T No 978 C-> No 1155 G ->T Yes 1359 A->G Yes 1682 G ->A No 1894 A->C No 1894 A ->G No 1953 A-> C No 2100 A ->C No 2103 A ->C No 2108 A ->T Yes 189 C-> No 2197 C ->A Yes 276 G -> A Yes 338 T-> No 424 G -> No WO 2005/072050 PCT/IB2005/000433 206 546 A ->G No 702 C ->T No 844 A ->G No 958 G-> No Variant protein T10888_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T10888_PEA_1_T5. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T10888_PEA__P5 and CEA6_HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_PS, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG 15 FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1 - 320 of CEA6_HUMAN, which also corresponds to amino acids I - 320 of T10888_PEA-1_P5, and a 20 second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV corresponding to amino acids 321 - 390 of T10888_PEAlP5, wherein said 25 first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 207 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KWIHALASHFQVESGSQRRARKKFSFPTCVQGAHIAIPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV in T10888-PEA_1_P5. 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal 10 peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans- membrane region downstream of this signal peptide.. Variant protein T10888_PEA_1_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the 15 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEAI_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 13 V-> No 232 N -> D No 63 I-> No 92 G-> No 20 Variant protein T10888_PEA-lP5 is encoded by the following transcript(s): T10888_PEA-1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA-lT5 is shown in bold; this coding portion starts at position 151 and ends at position 1320. The transcript also has the following SNPs as listed in WO 2005/072050 PCT/IB2005/000433 208 Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C ->T No 120 A ->T No 1062 A ->G Yes 1943 C ->A Yes 2609 C ->T Yes 2647 C ->G No 2701 C ->T Yes 2841 T->C Yes 189 C -> No 276 G -> A Yes 338 T-> No 424 G -> No 546 A -> G No 702 C->T No 844 A -> G No 930 C -> T Yes Variant protein T10888_PEA-lP6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 T10888_PEA_1_T6. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more WO 2005/072050 PCT/IB2005/000433 209 alignments to one or more previously published protein sequences are given at the end of tle application. Comparison report between T10888_PEA_1_P6 and CEA6_HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_P6, comprising a first 5 amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ NDTGFYTLQVIKSDLVNEEATGQFHVY corresponding to amino acids I - 141 of CEA6_HUMAN, which also corresponds to 10 amino acids 1 - 141 of T10888_PEA-lP6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI corresponding to amino acids 142 - 183 of T10888_PEA_1_P6, wherein said first and 15 second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI in 20 T10888_PEA_1_P6. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the 30 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888-PEA_1_P6 WO 2005/072050 PCT/IB2005/000433 210 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 13 V-> No 63 I-> No 92 G -> No 5 Variant protein T10888_PEA-lP6 is encoded by the following transcript(s): T10888_PEA_1-T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA-_T6 is shown in bold; this coding portion starts at position 151 and ends at position 699. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEALP6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C ->T No 120 A ->T No 189 C-> No 276 G ->A Yes 338 T-> No 424 G -> No 546 A -> G No 15 WO 2005/072050 PCT/IB2005/000433 211 As noted above, cluster T10888 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of 5 particular interest. A description of each segment according to the present invention is now provided. Segment cluster T10888-PEA_1_node_11 according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): T10888_PEA_1_TI and T10888_PEA_1_T5. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_TI 854 1108 T10888PEA_1_T5 854 1108 15 Segment cluster T10888_PEA_1_node_12 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_T5 1109 3004 20 Segment cluster T10888_PEA-1 node_17 according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA-1_TI and T10888_PEAIT4. Table 25 17 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 212 Table 17 - Segment location on transcripts Transcript name Segment starting position Segment emnlig position T10888_PEA_1_TI 1109 2518 T10888_PEA_1T4 967 2376 Segment cluster T10888_PEA_1_node_4 according to the present invention is supported 5 by 61 libraries. The number of libraries was determined as previously described. This segment can be found in.the following transcript(s): T10888-PEA_1 T1, T10888_PEA_1_T4, T10888-PEAIT5 and T10888_PEA_1_T6. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888 PEA_1_1 1 214 T10888_PEA_1 T4 1 214 T10888_PEA_1_T5 1 214 T10888_PEA_1_T6 1 214 10 Segment cluster T10888_PEAInode_6 according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEAITl, T10888_PEA_1_T4, 15 T10888_PEA_1_T5 and T10888_PEA_1_T6. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_1 215 574 T10888_PEA_1_T4 215 574 110888_PEA_1T5 215 574 WO 2005/072050 PCT/IB2005/000433 213 T10888_PEA_1_T6 215 574 Segment cluster T10888-PEAInode_7 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): T10888_PEA_1_T6. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_T6 575 1410 10 Segment cluster T10888_PEA_1_node_9 according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_Tl, T10888_PEA-lT4 and T10888_PEA-lT5. Table 21 below describes the starting and ending position of this segment on each transcript. 15 Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_Tl 575 853 T10888_PEA_1_T4 575 853 T10888_PEA_1_T5 575 853 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 20 Segment cluster T10888_PEA_1_node_15 according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA__T4. Table 22 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 214 Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_T4 854 966 Variant protein alignment to the previously known protein: Sequence name: /tmp/tM4EgaoKvm/vuztUrlRc7:CEA6_HUMAN 5 Sequence documentation: Alignment of: T10888_PEA_1_P2 x CEA6_HUMAN . . 10 Alignment segment 1/1: Quality: 3163.00 Escore: 0 Matching length: 319 Total 15 length: 319 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 20 Gaps: 0 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 2 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 WO 2005/072050 PCT/IB2005/000433 215 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 0 0 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 || || | |1 | | | | | | | | | || | | | | ||1 | l ii | | I 11| |111 | |I | I I||| | | | 5 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 10 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 15 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 301 AHNSATGLNRTTVTMITVS 319 20 301 AHNSATGLNRTTVTMITVS 319 Sequence name: /tmp/Yjllgj7TCe/PgdufzLOlW:CEA6_HUMAN 25 Sequence documentation: Alignment of: T10888_PEA_1_P4 x CEA6_HUMAN Alignment segment 1/1: 30 WO 2005/072050 PCT/IB2005/000433 216 Quality: 2310.00 Escore: 0 Matching length: 234 Total length: 234 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 15 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 li l l l l l l l l l l l1 1 ll l l l l l l l l l l l l l l l l l l l l l l l ll l l l l l l l l 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 20 . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 25 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 WO 2005/072050 PCT/IB2005/000433 217 Sequence name: /tmp/Yjllgj7TCe/PgdufzLOlW:Q13774 Sequence documentation: 5 Alignment of: T10888_PEA_1 P4 x Q13774 Alignment segment 1/1: Quality: 2310.00 10 Escore: 0 Matching length: 234 Total length: 234 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 25 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 WO 2005/072050 PCT/IB2005/000433 218 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 5 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 10 Sequence name: /tmp/x5xDBacdpj/rTXRGepv3y:CEA6_HUMAN Sequence documentation: Alignment of: T10888_PEA_1_P5 x CEA6_HUMAN 15 Alignment segment 1/1: Quality: 3172.00 Escore: 0 20 Matching length: 320 Total length: 320 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 25 Identity: 100.00 Gaps: 0 Alignment: 30 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 WO 2005/072050 PCT/IB2005/000433 219 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 5 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 10 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 15 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 20 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 301 AHNSATGLNRTTVTMITVSG 320 25 301 AHNSATGLNRTTVTMITVSG 320 Sequence name: /tmp/VAhvYFeatq/QNEM573uCo :CEA6_HUMAN Sequence documentation: 30 Alignment of: T10888_PEA_1 P6 x CEA6 HUMAN WO 2005/072050 PCT/IB2005/000433 220 Alignment segment 1/1: Quality: 1393.00 5 Escore: 0 Matching length: 143 Total length: 143 Matching Percent Similarity: 99.30 Matching Percent Identity: 99.30 10 Total Percent Similarity: 99.30 Total Percent Identity: 99.30 Gaps: 0 Alignment: 15 . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |l l 1l 1l1l l 1l l 1 l l 1ll 11ll1 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 20 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 | | | | | | | | | | | | | | I I I | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYRE 143 2 5 | | | | | | | | | | | | | | | | | | | | | 1 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPE 143 Alignment of: T10888_PEA_1_P6 x CEA6_HUMAN 30 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 221 Quality: 101.00 Escore: 0 Matching length: 141 Total length: 183 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 77.05 Total Percent Identity: 77.05 Gaps: 1 10 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 15 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 20 . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYREYFHMTSG 150 11lllllllllllllllllllll1llll1ll1lllllllll 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVY ......... .141 25 151 CWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI 183 141 ..................................................... 141 Expression of CEA6_HUMAN WO 2005/072050 PCT/IB2005/000433 222 Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888) transcripts which are detectable by anplicon as depicted in sequence name T10888 junc1 1-17 in normal and cancerous Breast tissues Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion 5 molecule 6 transcripts detectable by or according to junc1 1-17, T10888juncl 1-17 amplicon(s) and T10888junc11-17F and T10888juncI1-17R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), and SDHA (GenBank Accession No. NM_004168; amplicon 10 SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel", above), to 15 obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 7 is a histogram showing over expression of the above-indicated CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. 20 Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested, is indicated in the bottom. As is evident from Figure 7, the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in 25 cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel"). Notably an over-expression of at least 5 fold was found in 19 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. 30 The P value for the difference in the expression levels of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above WO 2005/072050 PCT/IB2005/000433 223 amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.OOE-03. Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 8.44B-03 as checked by exact fisher test. The above values 5 demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: T10888juncl 1-17F forward primer; and T 10888junc 11-1 7R reverse primer. 10 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T10888junc1 1 17. 15 T108S8junc I1-17F (SEQ ID NO:830) CCAGCAATCCACACAAGAGCT T10888junc I1-17R (SEQ ID NO:831) CAGGGTCTGGTCCAATCAGAG T10888juncl 1-17 (SEQ ID NO:832) 20 CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATAGC GGATCCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGGACCACAGT CACGATGATCACAGTCTCTGATTGGACCAGACCCTG 25 Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6T10888 transcripts which are detectable by amplicon as depicted in sequence name T10888juncl 1-17 in different normal tissues. 30 Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to T10888 juncl 1-17 amplicon(s) and T10888 WO 2005/072050 PCT/IB2005/000433 224 juncll-17F and T10888 juncll-17R was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL 19 (GenBank Accession No. NM_000981; RPL 19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession 5 No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2 "Tissue samples in normal panel" above), to obtain a value of relative expression of each sample relative to median 10 of the ovary samples. Primers and amplicon are as above. The results are presented in Figure 8, demonstrating the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888juncl 1-17, in different normal tissues. 15 DESCRIPTION FOR CLUSTER T39971 Cluster T39971 features 4 transcript(s) and 28 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 20 Table ] - Transcripts of interest Transcript Name Sequence ID No. T39971_TIO 18 T39971_T12 19 T39971_T16 20 T39971_T5 21 Table 2 - Segments of interest Segment Name Sequence ID No. T39971_node_0 22 WO 2005/072050 PCT/IB2005/000433 225 T39971_node 18 23 T39971_node_21 24 T39971_node_22 25 T39971_node 23 26 T39971_node_31 27 T39971_node_33 28 T39971_node_7 29 T39971_node 1 30 T39971_node_10 31 T39971_node_11 32 T39971_node_12 33 T39971_node_15 34 T39971_node_16 35 T39971_node_17 36 T39971_node_26 37 T39971_node_27 38 T39971_node_28 39 T39971_node_29 40 T39971_node 3 41 T39971_node_30 42 T39971-node_34 43 T39971_node_35 44 T39971_node_36 45 T39971_node_4 46 T39971_node_5 47 T39971-node_8 48 T39971_node_9 49 Table 3 - Proteins of interest WO 2005/072050 PCT/IB2005/000433 226 ProteinName Sequence ID No. T39971_P6 51 T39971_P9 52 T39971_Pll 53 T39971_P12 54 These sequences are variants of the known protein Vitronectin precursor (SwissProt accession identifier VTNCHUMAN; known also according to the synonyms Serum spreading factor; S-protein; V75), SEQ ID NO: 50, referred to herein as the previously known protein. 5 Protein Vitronectin precursor is known or believed to have the following function(s): Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interacts with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the me mbrane damaging effect of the terminal cytolytic complement pathway. The sequence for protein 10 Vitronectin precursor is given at the end of the application, as "Vitronectin precursor amino acid sequence" (SEQ ID NO:50). Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 122 A-> S. /FTId=VAR_012983. 268 R -> Q. /FTId=VAR_012984. 400 T -> M. /FTId=VAR_012985. 50 C->N 225 S->N 366 A->T Protein Vitronectin precursor localization is believed to be Extracellular. 15 The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer, melanoma. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct WO 2005/072050 PCT/IB2005/000433 227 therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Alphavbeta3 integrin antagonist; Apoptosis agonist. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field 5 because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anticancer. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: immune response; cell adhesion, which are annotation(s) related to 10 Biological Process; protein binding; heparin binding, which are annotation(s) related to Molecular Function; and extracellular space, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available 15 from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster T39971 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of 20 the table and the numbers on the y-axis of Figure 9 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 25 Figure 9 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: liver cancer, lung malignant tumors and pancreas carcinoma. Table 5 - Normal tissue distribution Name of Tissue Number adrenal 60 WO 2005/072050 PCT/IB2005/000433 228 bladder 0 Bone 0 Brain 9 Colon 0 epithelial 79 general 29 Liver 2164 Lung 0 lymph nodes 0 breast 0 pancreas 0 prostate 0 Skin 0 uterus 0 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 adrenal 6.9e-01 7.4e-01 2.0e-02 2.3 5.3e-02 1.8 bladder 5.4e-01 6.0e-01 5.6e-01 1.8 6.8e-0l 1.5 Bone I 6.7e-01 1 1.0 7.0e-01 1.4 Brain 8.0e-01 8.6e-01 3.0e-01 1.9 5.3e-01 1.2 Colon 4.2e-01 4.8e-01 7.0e-01 1.6 7.7e-01 1.4 epithelial 6.6e-01 5.7e-01 1.0e-01 0.8 8.7e-01 0.6 general 5.le-0I 3.8e-01 9.2e-08 1.6 8.3e-04 1.3 Liver 1 6.7e-01 2.3e-03 0.3 1 0.2 Lung 2.4e-01 9.le-02 1.7e-01 4.3 8.le-03 5.0 lymph nodes 1 5.7e-01 1 1.0 5.8e-01 2.3 breast 1 6.7e-01 1 1.0 8.2e-01 1.2 pancreas 9.5e-02 1.8e-01 1.5e- 11 6.5 8.2e-09 4.6 WO 2005/072050 PCT/IB2005/000433 229 prostate 7.3e-01 6.0e-01 6.7e-01 1.5 5.6e-01 1.7 Skin 1 4.4e-01 1 1.0 6.4e-01 1.6 uterus 5.0e-01 2.6e-01 1 1.1 8.0e-01 1.4 As noted above, cluster T39971 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Vitronectin precursor. A description of each variant protein according to the present invention is now provided. 5 Variant protein T39971_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T5. An alignment is given to the known protein (Vitronectin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the 10 application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T3997 1_P6 and VTNCHUMAN: 1.An isolated chimeric polypeptide encoding for T3997 1-P6, comprising a first amino acid sequence being at least 90 % homologous to 15 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino 20 acids 1 - 276 of VTNCHUMAN, which also corresponds to amino acids 1 - 276 of T39971_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90 % and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD corresponding to amino acids 277 - 283 of T39971-P6, wherein said first and second amino acid sequences are contiguous 25 and in a sequential order. 2.An isolated polypeptide encoding for a tail of T39971_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably WO 2005/072050 PCT/IB2005/000433 2 at least about 90% and most preferably at least about 95% homologous to the sequence TQGVVGD in T39971_P6. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 5 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T39971_P6 also has the following non-silent SNPs (Single Nucleotide 10 Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Prevlously known SNP? sequence 122 A->S Yes 145 G -> No 268 R->Q Yes 280 V -> A Yes ISO C -> No 180 C -> W No 192 Y -> No 209 A -> No 211 T-> No 267 G -> No 267 G->A No 268 R-> No 15 WO 2005/072050 PCT/IB2005/000433 231 Variant protein T39971_P6 is encoded by the following transcript(s): T39971_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T5 is shown in bold; this coding portion starts at position 756 and ends at position 1604. The transcript also has the following SNPs as listed in Table 8 (given according to their 5 position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 417 G -> C Yes 459 T-> C Yes 1387 C-> No 1406 ->A No 1406 ->G No 1555 G -> No 1555 G -> C No 1558 G -> No 1558 G -> A Yes 1594 T-> C Yes 1642 T-> C Yes 1770 C -> T Yes 529 G ->T Yes 1982 A ->G No 2007 G ->No 2029 T-> C No 2094 T->C No 2117 C -> G No 2123 C -> T Yes WO 2005/072050 PCT/IB2005/000433 232 2152 C ->T Yes 2182 G -> T No 2185 A-> C No 2297 T -> C Yes 1119 G->T Yes 2411 G -> No 2411 G->T No 2487 T -> C Yes 1188 G-> No 1295 C -> No 1295 C->G No 1324 ->T No 1331 C -> No 1381 C -> No Variant protein T39971_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T1O. An alignment 5 is given to the known protein (Vitronectin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T3997 1_P9 and VTNC_HUMAN: 1.An isolated chimeric polypeptide encoding for T39971_P9, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV 15 LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR

GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV

WO 2005/072050 PCT/IB2005/000433 233 LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids I - 325 of VTNCHUMAN, which also corresponds to amino acids 1 - 325 of T39971LP9, and a second amino acid sequence being at least 90 % homologous to 5 SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357 - 478 of VTNC-HUMAN, which also corresponds to amino acids 326 - 447 of T39971_P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 2.An isolated chimeric polypeptide encoding for an edge portion of T39971_P9, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a 15 structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326 + ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is belied to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T39971_P9 also has the following non-silent SNPs (Single Nucleotide 25 Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T3997 _P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 234 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 122 A ->S Yes 145 G-> No 268 R-> Q Yes 328 M->T No 350 S->P No 369 T -> M Yes 379 S->I No 380 N -> T No 180 C-> No 180 C -> W No 192 Y -> No 209 A -> No 211 T-> No 267 G-> No 267 G -> A No 268 R-> No Variant protein T39971_P9 is encoded by the following transcript(s): T39971_TI0, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T0I is shown in bold; this coding portion starts at position 756 and ends at position 5 2096. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T3997 1jP9 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 10 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 235 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 417 G -> C Yes 459 T->C Yes 1387 C-> No 1406 -> A No 1406 -> G No 1555 G -> No 1555 G->C No 1558 G -> No 1558 G->A Yes 1738 T -> C No 1803 T->C No 1826 C -> G No 529 G -> T Yes 1832 C -> T Yes 1861 C -> T Yes 1891 G->T No 1894 A -> C No 2006 T->C Yes 2120 G -> No 2120 G->T No 2196 T ->C Yes 1119 G ->T Yes 1188 G-> No 1295 C-> No 1295 C ->G No 1324 -> T No 1331 C -> No 1381 C-> No WO 2005/072050 PCT/IB2005/000433 236 Variant protein T39971_P11 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971-T12. An 5 alignment is given to the known protein (Vitronectin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T39971_P1 and VTNC_HUMAN: 1.An isolated chimeric polypeptide encoding for T3997 LP1 1, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV 15 LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1 - 326 of VTNC-HTMAN, which also corresponds to amino acids 1 - 326 of T39971_P11, and a second 20 amino acid sequence being at least 90 % homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442 - 478 of VTNC_HUMAN, which also corresponds to amino acids 327 - 363 of T39971_P11, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T39971Pl 1, 25 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and 30 ending at any of amino acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072050 PCT/IB2005/000433 237 Comparison report between T39971_P11 and Q9BSH7 (SEQ ID NO:833): 1.An isolated chimeric polypeptide encoding for T3997 1P 11, comprising a first amino acid sequence being at least 90 % homologous to 5 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE 10 CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids I - 326 of Q9BSH7, which also corresponds to amino acids 1 - 326 of T39971P1 1, and a second amino acid sequence being at least 90 % homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442 - 478 of Q9BSH7, which also corresponds to amino acids 327 - 363 of T39971_P11, wherein 15 said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T39971_P 1, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 20 least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327 + ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. 30 Variant protein T39971_P11 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid WO 2005/072050 PCT/IB2005/000433 238 sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T3997 1P 11 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 122 A -> S Yes 145 G-> No 268 R ->Q Yes 180 C-> No 180 C ->W No 192 Y-> No 209 A-> No 211 T-> No 267 G-> No 267 G->A No 268 R-> No 5 Variant protein T39971_P1 is encoded by the following transcript(s): T39971-T12, for which the sequence(s) is/are given at the end of the application. The coding portion of tramcript T39971_T12 is shown in bold; this coding portion starts at position 756 and ends at position 1844. The transcript also has the following SNPs as listed in Table 12 (given according to their 10 position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T3997 1_P1 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence WO 2005/072050 PCT/IB2005/000433 239 417 G->C Yes 459 T->C Yes 1387 C-> No 1406 -> A No 1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No 1558 G -> A Yes 1754 T->C Yes 1868 G -> No 1868 G->T No 529 G->T Yes 1944 T -> C Yes 1119 G->T Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No Variant protein T39971_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T16. An 5 alignment is given to the known protein (Vitronectin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 240 Comparison report between T39971_P12 and VTNC-UIJMAN: I .An isolated chimeric polypeptide encoding for T3997 1P 12, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC 5 KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1 - 223 of VTNCH-UMAN, which also corresponds to amino acids 1 - 223 of T39971P12, and a second amino acid sequence being at least 70%, optionally at least 80%, 10 preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 - 238 of T3997 1_P12, wherein said first ard second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T39971P12, comprising a polypeptide 15 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971_P12. Comparison report between T39971_P12 and Q9BSH7: 20 l.An isolated chimeric polypeptide encoding for T39971P12, comprising a first amino acid sequence being at least 90 % homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR 25 GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1 - 223 of Q9BSH7, which also corresponds to amino acids 1 - 223 of T39971P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV corresponding to amino acids 224 30 238 of T39971_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 241 2.An isolated polypeptide encoding for a tail of T39971_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV in T39971_P12. 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T39971_P12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is 15 known or not; the presence of known SNPs in variant protein T39971P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid nmtations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 122 A -> S Yes 145 G-> No 180 C-> No 180 C ->W No 192 Y-> No 209 A-> No 211 T-> No Variant protein T39971_P12 is encoded by the following transcript(s): T39971_T16, for 20 which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T16 is shown in bold; this coding portion starts at position 756 and ends at position WO 2005/072050 PCT/IB2005/000433 242 1469. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P12 sequence provides support for the deduced sequence of this variant protein 5 according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 417 G ->C Yes 459 T->C Yes 1387 C -> No 1406 -> A No 1406 -> G No 529 G -> T Yes 1119 G -> T Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No As noted above, cluster T39971 features 28 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) 10 are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. Segment cluster T3997 1_node_0 according to the present invention is supported by 76 15 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072050 PCT/IB2005/000433 243 found in the following transcript(s): T39971_T1O, T39971_T12, T39971_T16 and T39971_T5. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TIO 1 810 T39971T12 1 810 T39971_T16 1 810 T39971_T5 1 810 5 Segment cluster T39971_node_18 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T16. Table 16 below describes the starting and ending position of this segment on each transcript. 10 Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971I 16 1425 1592 Segment cluster T39971_node_21 according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): T39971_T10, T39971_T12 and T39971_T5. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T10 1425 1581 139971_T12 1425 1581 T39971_T5 1425 1581 WO 2005/072050 PCT/IB2005/000433 244 Segment cluster T39971_node_22 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5. Table 18 below describes the starting and 5 ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T5 1582 1779 Segment cluster T39971_node_23 according to the present invention is supported by 101 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10, T39971_T12 and T39971_T5. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TIO 1582 1734 T39971T12 1582 1734 T39971_T5 1780 1932 15 Segment cluster T39971_node_31 according to the present invention is supported by 94 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 and T39971_T5. Table 20 below describes the starting and ending position of this segment on each transcript. 20 Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T10 1847 1986 T39971_T5 2138 2277 WO 2005/072050 PCT/IB2005/000433 245 Segment cluster T39971_node_33 according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T39971_T1O, T39971_T12 and T39971_T5. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1987 2113 T39971_T12 1735 1861 T39971_T5 2278 2404 10 Segment cluster T39971-node_7 according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T1O, T39971 T12, T39971_T16 and T39971-T5. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcnpt name Segment starting position Segment ending position T39971-TI0 940 1162 T39971 Tl2 940 1162 T39971_T16 940 1162 T39971_T5 940 1162 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster T39971_node_1 according to the present invention can be found in the 20 following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971_T5. Table 23 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 246 Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T10 811 819 T39971_T12 811 819 T39971_T16 811 819 T39971_T5 811 819 Segment cluster T39971_node_10 according to the present invention is supported by 77 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971T5. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1189 1232 T39971_T12 1189 1232 T39971_T16 1189 1232 T39971_T5 1189 1232 10 Segment cluster T3997 1_node_11 according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971_T5. Table 25 below describes the starting and ending position of this segment on each transcript. 15 Table 25 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1233 1270 T39971_T12 1233 1270 T39971_T16 1233 1270 WO 2005/072050 PCT/IB2005/000433 247 T39971_T5 1233 1270 Segment cluster T39971_node_12 according to the present invention can be found in the following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971_T5. Table 26 5 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1271 1284 T39971_T12 1271 1284 T39971_T16 1271 1284 T39971_T5 1271 1284 Segment cluster T39971_node-15 according to the present invention is supported by 79 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10, T39971T12, T39971_T16 and T39971_T5. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TIO 1285 1316 T39971_T12 1285 1316 T39971_T16 1285 1316 T39971_T5 1285 1316 15 Segment cluster T39971_node_16 according to the present invention can be found in the following transcript(s): T39971_TIO, T39971_T12, T39971_T16 and T39971_T5. Table 28 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 248 Table 28 - Segment loca ,honz on transcripts Transcript name Segment starting position Segment ending position T39971_T10 1317 1340 T39971T12 1317 1340 T39971_Tl6 1317 1340 T39971_T5 1317 1340 Segment cluster T3997 1_node_17 according to the present invention is supported by 86 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T1O, T39971_T12, T39971_T16 and T39971_T5. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971T10 1341 1424 T39971_T12 1341 1424 T39971_T16 1341 1424 T39971_T5 1341 1424 10 Segment cluster T39971._node_26 according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5. Table 30 below describes the starting and ending position of this segment on each transcript. 15 Table 30 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T5 1933 1974 WO 2005/072050 PCT/IB2005/000433 249 Segment cluster T3997 1node27 according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T3997 1_T5. Table 31 below describes the starting and ending position of this segment on each transcript. 5 Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T5 1975 2025 Segment cluster T39971_node_28 according to the present invention can be found in the following transcript(s): T39971-T10 and T39971-T5. Table 32 below describes the starting and 10 ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TI0 1735 1743 T39971_T5 2026 2034 Segment cluster T39971_node_29 according to the present invention is supported by 99 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_TIO and T39971_T5. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TI 1744 1838 T39971_T5 2035 2129 20 WO 2005/072050 PCT/IB2005/000433 250 Segment cluster T3997 1_node_3 according to the present invention is supported by 78 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971-T1O, T39971_T12, T39971_T16 and T39971_T5. Table 34 below describes the starting and ending position of this segment on each transcript. 5 Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971-TI0 820 861 T39971_T12 820 861 T39971 T16 820 861 T39971-T5 820 861 Segment cluster T39971_node_30 according to the present invention can be found in the following transcript(s): T39971-T10 and T39971_T5. Table 35 below describes the starting and 10 ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1839 1846 T39971_T5 2130 2137 Segment cluster T39971_node_34 according to the present invention can be found in the 15 following transcript(s): T39971_T10, T39971_T12 and T39971_T5. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 2114 2120 T39971_T12 1862 1868 T39971_T5 2405 2411 WO 2005/072050 PCT/IB2005/000433 251 Segment cluster T39971_node_35 according to the present invention can be found in the following transcript(s): T39971-T10, T39971_T12 and T39971_T5. Table 37 below describes 5 the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment starting position Segnient ending position T39971_TIO 2121 2137 T39971_T12 1869 1885 T39971_T5 2412 2428 Segment cluster T39971_node_36 according to the present invention is supported by 51 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971-T10, T39971_T12 and T39971_T5. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 2138 2199 T39971_T12 1886 1947 T39971_T5 2429 2490 15 Segment cluster T39971_node_4 according to the present invention can be found in the following transcript(s): T39971_T1O, T39971_T12, T39971_T16 and T39971_T5. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971 TIO 862 881' WO 2005/072050 PCT/IB2005/000433 252 T39971T12 862 881 T39971T16 862 881 T39971T5 862 881 Segment cluster T39971-node_5 according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971_T5. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 882 939 T39971_T12 882 939 T39971_T16 882 939 T39971_T5 882 939 10 Segment cluster T39971_node_8 according to the present invention can be found in the following transcript(s): T39971_T10, T39971_T12, T39971_T16 and T39971_T5. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_T1O 1163 1168 T39971_T12 1163 1168 T39971_T16 1163 1168 T39971_T5 1163 1168 15 WO 2005/072050 PCT/IB2005/000433 253 Segment cluster T3997 1_node_9 according to the present invention can be found in the following transcript(s): T39971LT10, T39971_T12, T39971_T16 and T39971_T5. Table 42 below describes the starting and ending -position of this segment on each transcript. Table 42 - Segment location on transcripts Transcript name Segment starting position Segment ending position T39971_TIO 1169 1188 T39971.T12 1169 1188 T39971_T16 1169 1188 T39971_T5 1169 1188 5 Variant protein alignment to the previously known protein: 10 Sequence name: /tmp/xkraCL2OcZ/43L7YcPH7x:VTNCHUMAN Sequence documentation: Alignment of: T39971_P6 x VTNCHUMAN 15 Alignment segment 1/1: Quality: 2774.00 Escore: 0 20 Matching length: 278 Total length: 278 Matching Percent Similarity: 99.64 Matching Percent Identity: 99.64 Total Percent Similarity: 99.64 Total Percent 25 Identity: 99.64 WO 2005/072050 PCT/IB2005/000433 254 Gaps: 0 Alignment: 5 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 | |1 1| 1 1| | | | | | | I l l | | | | | | | | | 1|| | | | | | | 1| | | | | | | | | 1| | | 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 15 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 20 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 25 251 PDNVDAALALPAHSYSGRERVYFFKGTQ 278 251 PDNVDAALALPAHSYSGRERVYFFKGKQ 278 30 WO 2005/072050 PCT/IB2005/000433 255 Sequence name: /tmp/X4DeeuSlB4/yMubSR5FPs:VTNCHUMAN 5 Sequence documentation: Alignment of: T39971_P9 x VTNCHUMAN Alignment segment 1/1: 10 Quality: 4430.00 Escore: 0 Matching length: 447 Total length: 478 15 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 93.51 Total Percent Identity: 93.51 Gaps: 1 20 Alignment: 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 25 1 MAPLRPLLTILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKINATVHEQVGGPSLTS 100 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 30 - 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 WO 2005/072050 PCT/IB2005/000433 256 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 5 ||1|| 1|| 1|1|||| | | || || || || | 1| | || | 1 | | |||| 1||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 10 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 l i l l l I l i l il l lll l l l l l l l l l l l l l l l l 1| | | 1| | | | | | | | | | | | 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 15 - 301 VFEHFAMMQRDSWEDIFELLFWGRT ......................... 325 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 20 326 ...... SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 369 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400 370 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 419 25 | | | 1|1| 1111 | 1|1| |||| | | I | | | | | | | | | | | 1 ||| || 401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 420 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 447 30 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478 WO 2005/072050 PCT/IB2005/000433 257 5 Sequence name: /tmp/jvplVtnxNy/wxNSeFVZZw:VTNCHUMAN Sequence documentation: 10 Alignment of: T39971 P11 x VTNC HUMAN Alignment segment 1/1: Quality: 3576.00 15 Escore: 0 Matching length: 363 Total length: 478 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 20 Total Percent Similarity: 75.94 Total Percent Identity: 75.94 Gaps: 1 Alignment: 25 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 30 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 WO 2005/072050 PCT/IB2005/000433 258 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 | | | | | | | | | | | | | |1 1 1 1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | ||1 5 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||I l 11 I l l || I l lll 111 ll11|||| 1 l 1|||| |||1 1 ||||11 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 10 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 15 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 301 VFEHFAMMQRDSWEDIFELLFWGRTS ........................ 326 20 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 32 6 ....... ........ ....... ....... ..... ............ .... 3 26 25 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSAT 400 327 ..............................................

DKYYRVNLR 335 401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 30 . 336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363 WO 2005/072050 PCT/IB2005/000433 259 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478 5 Sequence name: /tmp/jvplVtnxNy/wxNSeFVZZw:Q9BSH7 10 Sequence documentation: Alignment of: T39971_P11 x Q9BSH7 15 Alignment segment 1/1: Quality: 3576.00 Escore: 0 Matching length: 363 Total 20 length: 478 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 75.94 Total Percent Identity: 75.94 25 Gaps: 1 Alignment: 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 3 0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 WO 2005/072050 PCT/IB2005/000433 260 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 1l i l l l l l l l l l l l 1 l l l l l l l l l l 1l l l l l l l 1| | | | | | | | | | | | | | | | | 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 5 - - 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 10 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 151 AEEELCSGKPFDAFTDLKGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 20 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 301 VFEHFAMMQRDSWEDIFELLFWGRTS ........................... 326 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 25 - 32 6 .. ...... ..... .... .. .. .. ... ..................... ... 3 2 6 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAM 400 30 327 ..............................................

DKYYRVNLR 335

|||||||||

WO 2005/072050 PCT/IB2005/000433 261 401 WLSLFSSEESNLGANYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363 lillllllllllllll1 I l lll l l I 5 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478 10 Sequence name: /tmp/fgebv7ir4i/48bTBMziJO:VTNCHUMAN Sequence documentation: 15 Alignment of: T39971_P12 x VTNCHUMAN Alignment segment 1/1: 20 Quality: 2237.00 Escore: 0 Matching length: 223 Total length: 223 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072050 PCT/IB2005/000433 262 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |1 |1 1 I | | | || |I | | | |1 I I1 | | | | | | | | |111 I | | | | | | | | || | | |1 | 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 5 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 1 0 | | | | | | | | | | | | | | | | | | | | | | | | 1 | | | | | | | | | | | | | | | | | | | ||1 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |1 ||||||||||111 |111 I I I 1I1I|I l I i||||||||||||||| 15 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 201 GIEGPIDAAFTRINCQGKTYLFK 223 201 GIEGPIDAAFTRINCQGKTYLFK 223 20 25 Sequence name: /tmp/fgebv7ir4i/48bTBMziJO :Q9BSH7 Sequence documentation: 30 Alignment of: T39971 P12 x Q9BSH7 WO 2005/072050 PCT/IB2005/000433 263 Alignment segment 1/1: Quality: 2237.00 Escore: 0 5 Matching length: 223 Total length: 223 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 25 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 30 201 GIEGPIDAAFTRINCQGKTYLFK 223 WO 2005/072050 PCT/IB2005/000433 264 201 GIEGPIDAAFTRINCQGKTYLFK 223 5 Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971 junc23-33 in normal and cancerous breast tissues Expression of VTNC_HUMVIAN vitronectin (serum spreading factor, somatomedin B, 10 complement S-protein) transcripts detectable by or according to junc23-33, T39971 junc23-33 amplicon and T39971 junc23-33F and T39971 junc23-33R primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon 15 SDHA-amplicon), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"), to 20 obtain a value of fold differetial expression for each sample relative to median of the normal PM samples. Figure 10 is a histogram showing down regulation of the above-indicated VTNCHUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts in cancerous breast samples relative to the normal samples. 25 As is evident from Figure 10, the expression of VTNC._HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by the above amplicon in cancer samples was significantly lower than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel"). Primer pairs are also optionally and preferably encompassed within the present 30 invention; for example, for the above experiment, the following primer pair was used as a non- WO 2005/072050 PCT/IB2005/000433 265 limiting illustrative example only of a suitable primer pair: T39971 junc23-33F forward primer; and T39971 junc23-33R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon 5 was obtained as a non- limiting illustrative example only of a suitable amplicon: T39971 junc23 33. T39971junc22-33F (SEQ ID NO:834): GGGGCAGAACCTCTGACAAG T39971junc22-33R (SEQ ID NO:835): GGGCAGCCCAGCCAGTA T39971junc22-33 amplicon (SEQ ID NO:836): 10 GGGGCAGAACCTCTGACAAGTACTACCGAGTCAATCTTCGCACACGGCGAGTGGAC ACTGTGGACCCTCCCTACCCACGCTCCATCGCTCAGTACTGGCTGGGCTGCCC Expression of VTNC_-HJMvAN vitronectin (serum spreading factor, somatomedin B, 15 complement S-protein), antisense to SARM1 (T23434), T39971 transcripts which are detectable by amplicon as depicted in sequence name T39971junc23-33 in different normal tissues Expression of VTNC_-HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), transcripts detectable by or according to T39971junc23-33 amplicon(s) 20 and T39971junc23-33F and T39971junc23-33R was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL 19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each 25 RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos. 33-35, Table 2, "Tissue samples in normal panel" above), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above. 30 WO 2005/072050 PCT/IB2005/000433 266 The results are presented in Figure 11, demonstrating the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARMI (T23434), T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971junc23-33, in different normal tissues. 5 Expression of VTNCHUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) T39971 transcripts which are detectable by amplicon as depicted in sequence name T39971 seg22 in normal and cancerous breast tissues Expression of VTNC_-HUMAN vitronectin (serum spreading factor, somatomedin B, 10 complement S-protein) transcripts detectable by or according to seg22, T39971 seg22 amplicon(s) and primers T39971 seg22F and T39971 seg22R was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRTI (GenBank Accession No. NM_000194; amplicon - HPRTl-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon 15 SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to 20 obtain a value of fold differential expression for each sample relative to median of the normal PM samples. In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a problem that is specific to this particular experiment.

WO 2005/072050 PCT/IB2005/000433 267 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: T39971 seg22F forward primer; and T39971 seg22R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: T39971 seg22. Forward primer T39971 seg22F (SEQ ID NO :837): 10 GCAGTCTTGGATTCCTTTCACATT Reverse primer T39971 seg22R (SEQ ID NO :838): GAGGCTGTTGAAGTTAGGATCTCC Amplicon T39971 seg22 (SEQ ID NO :839): GCAGTCTTGGATTCCTTTCACATTTCACTGGGGACAGGCCTCAGCATGTGCCCACCC 15 CTGACCCCCACCTCATGCTGGGAGATCCTAACTTCAACAGCCTC DESCRIPTION FOR CLUSTER Z21368 20 Cluster Z21368 features 7 transcript(s) and 34 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. Z21368_PEA1_-T10 55 Z21368_PEA_1_11 56 Z21368_PEA_1_T23 57 Z21368_PEAlT24 58 Z21368_PEAl_T5 59 Z21368_PEA_1_T6 60 WO 2005/072050 PCT/IB2005/000433 268 Z21368_PEA_1_T9 61 Table 2 - Segments of interest Segment Name Sequence 1D No. Z21368_PEAInode_0 62 Z21368_PEA_1_node_15 63 Z21368_PEA_1_node_19 64 Z21368_PEA1_node_2 65 Z21368_PEA 1 node_21 66 Z21368_PEA_1_node_33 67 Z21368_PEA1_node_36 68 Z21368_PEA_1_node_37 69 Z21368_PEA_1_node_39 70 Z21368_PEA_1_node_4 71 Z21368_PEA_1_node_41 72 Z21368_PEA_1_node_43 73 Z21368_PEA_1_node_45 74 Z21368_PEA_1_node_53 75 Z21368_PEA_1-node_56 76 Z21368_PEA_1_node_58 77 Z21368_PEA_1_node_66 78 Z21368_PEA_1_node_67 79 Z21368_PEA_1_node_69 80 Z21368_PEA 1 node-11 81 Z21368_PEAInode_12 82 Z21368_PEA_1_node_16 83 Z21368_PEA_1_node_17 84 Z21368_PEA_1_node_23 85 Z21368_PEA_1_node_24 86 WO 2005/072050 PCT/IB2005/000433 269 Z21368-PEA_1_node_30 87 Z21368_PEA_1_node_31 88 Z21368_PEA_1node_38 89 Z21368_PEA1_node_47 90 Z21368_PEA_1_node_49 91 Z21368_PEA1_node_51 92 Z21368_PEA_1_node_61 93 Z21368_PEA 1_node 68 94 Z21368_PEA 1 node 7 95 Table 3 - Proteins of interest Protein Name Sequence ID No. Z21368_PEA_1_P2 97 Z21368_PEA_1 P5 98 Z21368_PEA_1 P15 99 Z21368_PEA-1-P16 100 Z21368_PEA_1_P22 101 Z21368_PEA_1_P23 102 These sequences are variants of the known protein Extracellular sulfatase Sulf- 1 precursor 5 (SwissProt accession identifier SUL1I-HUMAN; known also according to the synonyms EC 3.1.6.-; HSulf- 1), SEQ ID NO: 96, referred to herein as the previously known protein. Protein Extracellular sulfatase Sulf- 1 precursor is known or believed to have the following function(s): Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions 10 of intact heparin. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation. The sequence for protein Extracellular sulfatase Sulf- 1 precursor is given at the end of the application, as "Extracellular sulfatase Sulf- 1 precursor WO 2005/072050 PCT/IB2005/000433 270 amino acid sequence" (SEQ ID NO:96). Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 87- 88 CC->AA: LOSS OF ARYLSULFATASE ACTIVITY AND LOSS OF ABILITY TO MODULATE APOPTOSIS. 49 L->P 728 K->R 5 Protein Extracellular sulfatase Sulf- 1 precursor localization is believed to be Endoplasmic reticulum and Golgi stack; also localized on the cell surface (By similarity). The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: apoptosis; metabolism; heparan sulfate proteoglycan metabolism, which are annotation(s) related to Biological Process; arylsulfatase; hydrolase, which are 10 annotation(s) related to Molecular Function; and extracellular space; endoplasmic reticulum; Golgi apparatus, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 15 Cluster Z21368 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of Figure 12 refer to weighted expression of ESTs in 20 each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 12 and Table 5. This cluster is overexpressed (at least at a minimum level) in the WO 2005/072050 PCT/IB2005/000433 271 following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. Table 5 - Nernnal tissue distribution Name of Tissue Number bladder 123 Bone 557 Brain 34 Colon 94 epithelial 56 general 68 head and neck 0 kidney 35 Lung 22 lymph nodes 0 breast 52 muscle 31 ovary pancreas 0 prostate 44 skin 67 stomach 109 T cells 0 Thyroid 0 uterus 140 5 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 bladder 5.4e-01 6.6e-01 6.4e-01 1.0 8.5e-0l 0.7 bone 4.5e-01 8.2e-01 9.le-01 0.4 1 0.3 WO 2005/072050 PCT/IB2005/000433 272 brain 5.5e-01 7.3e-01 1.5e-01 1.5 5.0e-01 0.9 colon 1.4e-01 2.8e-01 l.Oe-01 2.0 3.0e-01 1.4 epithelial 1.le-03 1.5e-01 1.2e-07 2.1 1.Oe-01 1.1 general 1.4e-05 5.3e-02 1.9e-06 1.6 6.7e-01 0.8 head and neck 2.4e-02 7.le-02 4.6e-01 2.5 7.5e-01 1.4 kidney 8.9e-01 9.0e-01 1 0.4 1 0.4 lung 3.5e-01 4.le-01 7.2e-03 2.6 1.0e-01 1.6 lymph nodes 7.7e-02 3.le-01 2.3e-02 8.5 1.9e-01 3.2 breast 4.0e-01 6.le-01 5.4e-02 2.3 3.0e-01 1.3 muscle 7.5e-02 3.5e-02 1 1.0 1.7e-01 1.7 ovary 3.8e-01 4.2e-01 2.2e-01 2.9 3.4e-01 2.2 pancreas 2.2e-02 6.9e-02 1.4e-08 6.5 1.4e-06 4.6 prostate 8.3e-01 8.9e-01 3.le-01 1.4 5.2e-01 1.1 skin 6.le-01 8.le-01 6.0e-01 1.2 1 0.3 stomach 4.4e-02 5.0e-01 5.0e-01 0.8 9.7e-01 0.4 T cells 5.0e-01 6.7e-01 3.3e-01 3.1 7.2e-01 1.4 Thyroid 3.6e-0l 3.6e-01 1 1.1 1 1.1 uterus 3.5e-01 7.8e-01 4.6e-01 0.9 9.le-01 0.5 As noted above, cluster Z21368 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Extracellular sulfatase Sulf- 1 precursor. A description of each variant protein according to the present 5 invention is now provided. Variant protein Z21368_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA_1_T5. An alignment is given to the known protein (Extracellular sulfatase Sulf-1 10 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 273 Comparison report between Z21368_PEA_1_P2 and SULl-HUMAN: 1.An isolated chimeric polypeptide encoding for Z21368_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNILVLTDDQDVELGSL 5 QVNNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSPJYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMSHAAPHGPEDSAPQ FSKLYPNASQHTPSYNYAPNMDKHWIMQYTGPMLPIMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP 10 GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNELPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQ GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI 15 DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN corresponding to amino acids 1 - 761 of SUL LHUMAN, which also corresponds to amino acids 1 - 761 of Z21368_PEAlP2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI corresponding to amino acids 762 - 790 of Z21368-PEAlP2, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z21368_PEALP2, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI in Z21368_PEA_1_P2. The location of the variant protein was determined according to results from a number of 30 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: WO 2005/072050 PCT/IB2005/000433 274 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein Z21368_PEA_1_P2 is encoded by the following transcript(s): 5 Z21368_PEA_-T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA_1_T5 is shown in bold; this coding portion starts at position 529 and ends at position 2898. Variant protein Z21368_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 Z21368_PEA-_T9. An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 15 Comparison report between Z21368-PEAI_P5 and Q7Z2W2 (SEQ ID NO:840): 1 .An isolated chimeric polypeptide encoding for Z21368-PEA_1-P5, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL 20 corresponding to amino acids I - 57 of Q7Z2W2, which also corresponds to amino acids 1 - 57 of Z21368_PEA_1_P5, second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYF TDLITN ESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNM 25 DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFE 30 GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT

TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR

WO 2005/072050 PCT/IB2005/000433 275 RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCN PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139 - 871 of 5 Q7Z2W2, which also corresponds to amino acids 59 - 791 of Z21368_PEA_1_P5, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of Z21368_PEA_1_P5, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 10 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEAlP5): a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 59 + ((n-2) - x), in which x varies from 0 to n-2. 15 Comparison report between Z21368_PEA-1_P5 and AAH12997 (SEQ ID NO:841): I An isolated chimeric polypeptide encoding for Z21368_PEA_1_P5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP 25 DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMIADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK 30 PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE

KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH

WO 2005/072050 PCT/IB2005/000433 276 NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME corresponding to amino acids 1 - 751 of Z21368_PEA_1_P5, and a second amino acid sequence being at least 90 % homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1 - 40 of AAH12997, which also corresponds to amino acids 752 5 791 of Z21368_PEA-_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of Z21368_PEA_lP5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 9 0% and most preferably at least about 95% homologous to the 10 sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD 15 HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV 20 RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSEQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNTWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME of Z21368_PEA_1-P5. 25 Comparison report between Z21368_PEA__P5 and SULlIHUMAN: 1.An isolated chimeric polypeptide encoding for Z21368-PEA_1_P5, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1 - 57 of SUL l_I-HMAN, which also corresponds to amino acids 30 1 - 57 of Z21368_PEA_1_P5, and a second amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 277 AFFGKYLNEYNGSYIPFGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYP HRPVMMVISHAAPHGPEDSAPQFSKLYPNASQIJ1TPSYNYAPN MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYH YTADHGYMGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL 5 DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVE FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFDWPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL 10 KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYK QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138 - 871 of SUL l_-JHUMAN, which also corresponds to amino acids 58 - 791 of Z21368-PEA_1_P5, 15 wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of Z21368_PEA_1_P5, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 20 least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 58 + ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. 30 Variant protein Z21368_PEA-lP5 is encoded by the following transcript(s): Z21368_PEA_IT9, for which the sequence(s) is/are given at the end of the application. The WO 2005/072050 PCT/IB2005/000433 278 coding portion of transcript Z21368_PEA_1_T9 is shown in bold; this coding portion starts at position 556 and ends at position 2928. Variant protein Z21368_PEA_1_P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Z21368_PEA_1_T23. An alignment is given to the known protein (Extracellular sulfatase Sulf 1 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Z21368_PEA_1_P15 and SULl_HUMAN: 1.An isolated chimeric polypeptide encoding for Z21368_PEA_1_P15, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW 15 QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESlNYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMILPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL 20 VERG corresponding to amino acids 1 - 416 of SULl_HUMAN, which also corresponds to amino acids I - 416 of Z21 368 _PEA 1_P15. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein Z21368_PEA_1_P15 is encoded by the following transcript(s): Z21368_PEAlT23, for which the sequence(s) is/are given at the end of the application. The 30 coding portion of transcript Z21368_PEA_1_T23 is shown in bold; this coding portion starts at position 691 and ends at position 1938.

WO 2005/072050 PCT/IB2005/000433 279 Variant protein Z21368_PEA_1-P16 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA_1_T24. An alignment is given to the known protein (Extracellular sulfatase Sulf 1 precursor) at the end of the application. One or more alignments to one or more previously 5 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z21368_PEA_1_P16 and SUL1_HUMAN: 10 l.An isolated chimeric polypeptide encoding for Z21368_PEA-_1P16, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR 15 NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1 - 397 of SULl_I-HIUMAN, which also corresponds to amino acids I - 397 of 20 Z21368_PEA_1_P16, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CVIVPPLSQPQIH corresponding to amino acids 398 - 410 of Z21368_PEA_1_P16, wherein said first and second amino acid sequences are contiguous and in a seque ntial order. 25 2.An isolated polypeptide encoding for a tail of Z21368_PEA_1_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH in Z21368_PEA_1_P16. 30 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized WO 2005/072050 PCT/IB2005/000433 280 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 5 Variant protein Z21368_PEA_1_P16 is encoded by the following transcript(s): Z21368_PEAlT24, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA_1_T24 is shown in bold; this coding portion starts at position 691 and ends at position 1920. Variant protein Z21368_PEA_1_P22 according to the present invention has an amino acid 10 sequence as given at tfi end of the application; it is encoded by transcript(s) Z21368_PEA-1_T10. An alignment is given to the known protein (Extracellular sulfatase Sulf 1 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein 15 is as follows: Comparison report between Z21368_PEA_1_P22 and SULl_HUMAN: 1.An isolated chimeric polypeptide encoding for Z21368_PEAlP22, comprising a first amino acid sequence being at least 90 % homologous to 20 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNJRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVIHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1 - 188 of SULl_HUMAN, which also corresponds to amino acids 1 - 188 of Z21368_PEA-lP22, and a second amino acid sequence 25 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF corresponding to amino acids 189 - 210 of Z21368_PEA_1_P22, wherein said first and second amino acid sequences are contiguous and in a sequential order. 30 2.An isolated polypeptide encoding for a tail of Z21368_PEA_1_P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 281 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGLSPTVF in Z21368_PEA_1_P22. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein Z21368-PEA_1_P22 is encoded by the following transcript(s): Z21368_PEA_1-T 10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA_._TIO is shown in bold; this coding portion starts at position 691 and ends at position 1320. 15 Variant protein Z21368_PEA_1_P23 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA_1_TI 1. An alignment is given to the known protein (Extracellular sulfatase Sulf 1 precursor) at the end of the application. One or more alignments to one or more previously 20 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z21368_PEA_1_P23 and Q7Z2W2: 25 1.An isolated chimeric polypeptide encoding for Z21368_PEAlP23, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1 - 137 of Q7Z2W2, which also 30 corresponds to amino acids I - 137 of Z21368_PEA_1_P23, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least WO 2005/072050 PCT/IB2005/000433 282 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH corresponding to amino acids 138 - 145 of Z21368_PEA-_1P23, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z21368_PEA_1_P23, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23. Comparison report between Z21368_PEA-lP23 and SULI_HIHUMAN: 10 1.An isolated chimeric polypeptide encoding for Z21368_PEA_1_P23, comprising a first amino acid sequence being at least 90 % homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1 - 137 of SULl_HUMAN, 15 which also corresponds to amino acids I - 137 of Z21368_PEA_1_P23, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNIH corresponding to amino acids 138 - 145 of Z21368_PEA-1_P23, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2)0 2.An isolated polypeptide encoding for a tail of Z21368_PEA-_1 P23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH in Z21368_PEA_1_P23. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 30 region prediction program predicts that this protein has a trans-membrane region.

WO 2005/072050 PCT/IB2005/000433 283 Variant protein Z21368_PEA_1-P23 is encoded by the following transcript(s): Z21368_PEA_1-T 11, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA-1_T 1I is shown in bold; this coding portion starts at position 691 and ends at position 1125. 5 As noted above, cluster Z21368 features 34 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 10 Segment cluster Z21368_PEA_1_node_0 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA-lT9. Table 7 below describes the starting and ending position of this segment on each transcript. 15 Table 7 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368-PEA-lT9 1 327 Segment cluster Z21368_PEA-_node_15 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368_PEAlTLL, Z21368_PEA._1T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA lT9. Table 8 below describes the starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEAI_TIO 631 807 Z21368_PEA_1_TI1 631 807 WO 2005/072050 PCT/IB2005/000433 284 Z21368_PEA_1_T23 631 807 Z21368_PEA_1_T24 631 807 Z21368_PEA_1_T5 469 645 Z21368-PEA_1_T6 469 645 Z21368_PEA_1_T9 496 672 Segment cluster Z21368_PEAInode_19 according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368_PEA_1_T 1, Z21368_PEAlT23, Z21368_PEAlT24, Z21368_PEA_1_T5 and Z21368_PEA__T6. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_TIO 863 1102 Z21368-PEA_ IT11 863 1102 Z21368_PEA_1_T23 863 1102 Z21368-PEA__T24 863 1102 Z21368_PEA_1T5 701 940 Z21368_PEA_1_T6 701 940 10 Segment cluster Z21368_PEAInode_2 according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA_1_T1O, Z21368_PEA1-T1 1, Z21368_PEA_1_T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5 and Z21368_PEA_1_T6. 15 Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name' Segment starting position Segment ending position WO 2005/072050 PCT/IB2005/000433 295 Z21368_PEA_1T10 1 300 Z21368_PEA_1_Til 1 300 Z21368_PEA_1_T23 1 300 Z21368_PEA_1_T24 1 300 Z21368_PEA_1_T5 1 300 Z21368_PEA_1_T6 1 300 Segment cluster Z21368_PEA-_1node_21 according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368-PEA_1_TI, Z21368-PEA_1_T23, Z21368_PEA-_-T24, Z21368-PEA-lT5, Z21368_PEA 1_T6 and Z21368_PEA-_T9. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment starting position Sement ending position Z21368-PEA-1_T10 1103 1254 Z21368_PEAl-T23 1103 1254 Z21368_PEA_1-T24 1103 1254 Z21368_PEA__T5 941 1092 Z21368_PEA_1_T6 941 1092 Z21368_PEA__T9 728 879 10 Segment cluster Z21368_PEA_1-node_33 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA_1_TIO, Z21368-PEA_1_T11, Z21368_PEAlT23, Z21368_PEA-lT24, Z21368-PEAl_T5, Z21368-PEA_1_T6 and 15 Z21368_PEA_1_T9. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 286 Transcript name Segment starting position Segment ending position Z21368_PEA 1_T1O 1502 1677 Z21368_PEAI_T 1l 1424 1599 Z21368_PEA_lT23 1576 1751 Z21368_PEA_1 T24 1576 1751 Z21368_PEAlT5 1414 1589 Z21368_PEA_1_T6 1414 1589 Z21368_PEA_1T9 12011376 Segment cluster Z21368_PEA_1_node-36 according to the present invention is supported by 44 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1_T1O, Z21368_PEA_1_T11, Z21368_PEAlT23, Z21368_PEAlT24, Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA_1_T9. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position 721368_PEA-1_T1O 1678 1806 Z21368_PEA-_1 T 11 1600 1728 Z21368_PEA_1T23 1752 1880 Z21368-PEA_1_T24 1752 1880 Z21368_PEA_1_T5 1590 1718 Z21368_PEA_1_T6 1590 1718 Z21368_PEA_1_T9 1377 1505 10 Segment cluster Z21368_PEA_1-node_37 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 287 can be found in the following transcript(s): Z21368-PEA_1_T24. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T24 1881 2159 5 Segment cluster Z2 1368_PEA__node_39 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T23 and Z21368_PEA-lT24. Table 15 below describes the starting and ending position of this segment on each transcript. 10 Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T23 1938 2790 Z21368_PEA__T24 2217 3069 Segment cluster Z21368_PEA_1_node_4 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Z21368PEAiTlO, Z21368_PEA-1_TI 1, Z21368_PEA_1_T23 and Z21368_PEA_1-T24. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA-_1T1O 301 462 Z21368-PEA_1 T11 301 462 Z21368_PEA-1_T23 301 462 Z21368_PEA_1_T24 301 462 WO 2005/072050 PCT/IB2005/000433 288 Segment cluster Z21368_PEA_1_node_41 according to the present invention is supported by 49 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_TIO, Z21368_PEA_1_T11, 5 Z21368_PEA-lT5, Z21368_PEA_1-T6 and Z21368_PEA_1_T9. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position' Z21368PEA_1_T1O 1864 1993 Z21368_PEA_1_Tl 1 1786 1915 Z21368_PEAlT5 1776 1905 Z21368_PEA_1_T6 1776 1905 Z21368_PEA_1_T9 1563 1692 10 Segment cluster Z21368_PEA_1_node_43 according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEAlLT10, Z21368_PEAL-T1 1, Z21368_PEAL-T5, Z21368_PEA_1_T6 and Z21368_PEA_1_T9. Table 18 below describes the starting and ending position of this segment on each transcript. 15 Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA-1_T1O 1994 2210 Z21368-PEA_1_T l1 1916 2132 Z21368_PEA_1_T5 1906 2122 Z21368_PEA_1_T6 1906 2122 Z21368_PEA-1_T9 1693 1909 WO 2005/072050 PCT/IB2005/000433 289 Segment cluster Z21368_PEA-1_node_45 according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1TIO, Z21368_PEA_1_TI1, Z21368_PEA_1_T5, Z21368_PEA-lT6 and Z21368_PEA_1_T9. Table 19 below describes 5 the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name. Segment starting position Segment ending position Z21368_PEA_1_T1O 2211 2466 Z21368_PEAI Tl l 2133 2388 Z21368_PEA__T5 2123 2378 Z21368_PEAI-T6 2123 2378 Z21368_PEA-lT9 1910 2165 Segment cluster Z21368_PEA_1_node_53 according to the present invention is supported 10 by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEAlT1O, Z21368-PEALT1 1, Z21368_PEAlT5, Z21368_PEA__T6 and Z21368-PEA__T9. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T10 2725 2900 Z21368_PEA IT ll 2647 2822 Z21368_PEAiT5 2637 2812 Z21368_PEA_1_T6 2637 2812 Z21368_PEA_1_T9 2424 2599 15 WO 2005/072050 PCT/IB2005/000433 290 Segment cluster Z21368_PEA_1Inode_56 according to the- present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1 TIO, Z21368_PEA_1-T 1I and Z21368_PEA_1_T9. Table 21 below describes the starting and ending position of this segment 5 on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA-1 TIO 2901 3043 Z21368_PEA_1_Tll 2823 2965 Z21368-PEA_1_T9 2600 2742 Segment cluster Z21368_PEA-_1node_58 according to the present invention is supported 10 by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_TIO, Z21368_PEAL-Tl 1, Z21368_PEA-lT5, Z21368_PEAlT6 and Z21368_PEA_1_T9. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts :Transcript name Segment starting position Segment ending position Z21368-PEA_1-TI0 3044 3167 Z21368_PEA_1 T11 2966 3089 Z21368_PEA_ T5 2813 2936 Z21368_PEA_1_T6 2813 2936 Z21368_PEA-lT9 2743 2866 15 Segment cluster Z21368_PEA_1_node_66 according to the present invention is supported by 142 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368_PEA_1_T11, WO 2005/072050 PCT/IB2005/000433 291 Z21368_PEA_1_T5, Z21368-PEA_1_T6 and Z21368PEA-lT9. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment. starting position Segment ending position Z21368_PEA_1_T1O 3202 3789 Z21368_PEA_1_TIl 3124 3711 Z21368-PEA_lT5 2971 3558 Z21368_PEA_1_T6 2971 3558 Z21368-PEA_1-T9 2901 3488 5 Segment cluster Z21368_PEA_1_node_67 according to the present invention is supported by 181 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368_PEA_1_TI 1, Z21368_PEA-lT5, Z21368_PEA__T6 and Z21368_PEA_1_T9. Table 24 below describes 10 the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Trans cript name Segment starting position Segment ending position Z21368_PEA_1_T1O 3790 4374 Z21368_PEA I_T11 3712 4296 Z21368_PEA_1_T5 3559 4143 Z21368_PEA_1_T6 3559 4143 Z21368_PEA_1_T9 3489 4073 Segment cluster Z21368_PEA_1_node_69 according to the present invention is supported 15 by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T1O, Z21368_PEA1_T1 1, WO 2005/072050 PCT/IB2005/000433 292 Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA_1-T9. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transdript name Segment starting position Segment ending position Z21368_PEA_1_T1O 4428 4755 Z21368_PEA_1Tll 4350 4677 Z21368_PEA_1_T5 4197 5384 Z21368_PEA_1_T6 4197 4524 Z21368_PEA_1_T9 4127 4454 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster Z2 1368_PEA_1_node_11 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): Z21368_PEAL-TO, Z21368_PEA-1_TI 1, Z21368_PEA_1-T23, Z21368_PEA_1_T24, Z21368_PEA-lT5, Z21368PEA_1_T6 and Z21368 PEA-1_T9. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T1O 558 602 Z21368PEA_1 Til 558 602 Z21368_PEA_T23 558 602 Z21368_PEA_1_T24 558 602 Z21368_PEA_1_T5 396 440 Z21368_PEA_1_T6 396 440 Z21368_PEA_1_T9 423 467 15 WO 2005/072050 PCT/IB2005/000433 293 Segment cluster Z21368_PEA_1_node_12 according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEALT1O, Z21368_PEA_1_Tll, 5 Z21368_PEA_1-T23, Z21368_PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA_1-T9. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T1O 603 630 Z21368_PEA 1 Tll 603 630 Z21368_PEA 1_T23 603 630 Z21368_PEA_1 T24 603 630 Z21368_PEA_1_T5 441 468 Z21368_PEA IT6 441 468 Z21368_PEA_1 T9 468 495 10 Segment cluster Z21368_PEA_1_node_16 according to the present invention can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368-PEA-1_TI 1, Z21368-PEAIT23, Z21368_PEA-l-T24, Z21368_PEA_1_T5, Z21368_PEA-lT6 and Z21368_PEA-1_T9. Table 28 below describes the starting and ending position of this segment 15 on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA-1_T1O 808 822 Z21368_PEA_1_Tl 808 822 Z21368_PEA1 T23 808 822 Z21368_PEA_1_T24 808 822 WO 2005/072050 PCT/IB2005/000433 294 Z21368_PEA_1_T5 646 660 Z21368_PEA-lT6 646 660 Z21368_PEA_1_T9 673 687 Segment cluster Z21368_PEA_1_node-17 according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368_PEA_1_Ti1, Z21368_PEA_1-T23, Z21368-PEA_1_T24, Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA lT9. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA 1_TIO 823 862 Z21368_PEA_1_Tll 823 862 Z21368_PEA_1 T23 823 862 Z21368_PEA_1 T24 823 862 Z21368-PEA_1_T5 661 700 Z21368_PEA_1_T6 661 700 Z21368-PEA_1_T9 688 727 10 Segment cluster Z21368_PEA_1_node_23 according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEALT1 1, Z21368_PEA_1_T23, 15 Z21368_PEA_1_T24, Z21368_PEA-l-T5, Z21368-PEA_1_T6 and Z21368_PEA_1_T9. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072050 PCT/IB2005/000433 295 Z21368_PEA 1 TIl 1103 1176 Z21368_PEA 1T23 1255 1328 Z21368_PEA_1_T24 1255 1328 Z21368_PEA1 T5 1093 1166 Z21368_PEA 1 T6 1093 1166 Z21368_PEAIT9 880 953 Segment cluster Z21368-PEA_1_node_24 according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1_TI0, Z21368_PEA_1_Ti1, Z21368-PEA_1_T23, Z21368_PEALT24, Z21368_PEAJJT5, Z21368_PEA_1_T6 and Z21368_PEA_1_T9. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA1 T10 1255 1350 Z21368_PEA 1 T11 1177 1272 Z21368_PEA 1 T23 1329 1424 Z21368_PEA 1_T24 1329 1424 Z21368_PEAIT5 1167 1262 Z21368_PEA_1_T6 1167 1262 Z21368_PEA_1_T9 954 1049 10 Segment cluster Z21368_PEA-1-node_30 according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA_1-T10, Z21368_PEAL-T1 1, 15 Z21368_PEA_ lT23, Z21368_PEA_1T24, Z21368_PEA_1_T5, Z21368_PEA_1-T6 and WO 2005/072050 PCT/IB2005/000433 296 Z21368_PEA_1-T9. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T10 1351 1409 Z21368_PEA_1 Tl 1273 1331 Z21368_PEA_1_T23 1425 1483 Z21368_PEA_1_T24 1425 1483 Z21368_PEAI T5 1263 1321 Z21368_PEA_1_T6 1263 1321 Z21368_PEA_1_T9 1050 1108 5 Segment cluster Z2 1368_PEA- Inode_31 according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_TIO, Z21368_PEA_1_ 11, Z21368-PEA_1_T23, Z21368-PEA1 _T24, Z21368_PEA-lT5, Z21368_PEA_1_T6 and 10 Z21368_PEA_1_T9. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1 T10 1410 1501 Z21368_PEA_1 111 1332 1423 Z21368_PEA_1_T23 1484 1575 Z21368_PEA.1 T24 1484 1575 Z21368_PEA_1_T5 1322 1413 Z21368_PEA_1_T6 1322 1413 Z21368_PEA_1_T9 1109 1200 WO 2005/072050 PCT/IB2005/000433 297 Segment cluster Z21368_PEA-_1node_38 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T10, Z21368-PEA_1_TI 1, 5 Z21368_PEA_-T23, Z21368_PEA_1_T24, Z 2 1368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368-PEA_1_T9. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368-PEA_1_TIO 1807 1863 Z21368_PEA_1_TIl 1729 1785 Z21368_PEA_1_T23 1881 1937 Z21368_PEAlT24 2160 2216 Z21368_PEA_1_T5 1719 1775 Z21368_PEAIT6 1719 1775 Z21368_PEAIT9 1506 1562 10 Segment cluster Z21368-PEA_1_node_47 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA_1_TIO, Z21368_PEA-1_TlI, Z21368_PEA_1_T5, Z21368_PEA_1_T6 and Z21368-PEA_1_T9. Table 35 below describes 15 the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1 TI0 2467 2563 Z21368_PEA_1_Tll 2389 2485 Z21368_PEA_1_T5 2379 2475 Z21368_PEA _T6 2379 2475 WO 2005/072050 PCT/IB2005/000433 298 Z21368_PEA-1_T9 2166 2262 Segment cluster Z21368_PEALnode_49 according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1-T10, Z21368_PEA_1_T11, Z21368_PEAIT5, Z21368_PEA_1_T6 and Z21368_PEA_1_T9. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1 T10 2564 2658 Z21368_PEA_1_11 2486 2580 Z21368_PEA1._T5 2476 2570 Z21368_PEA_1_T6 2476 2570 Z21368_PEA_1_T9 2263 2357 10 Segment cluster Z21368_PEA_1_node_51 according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA-1-T10, Z21368_PEA-_T11, Z21368_PEA_1_T5, Z21368_PEA-lT6 and Z21368-PEA_1_T9. Table 37 below describes 15 the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_T10 2659 2724 Z21368-PEA_ 1_TI1 2581 2646 Z21368_PEA_1_T5 2571 2636 Z21368_PEA_1_T6 2571 2636 Z21368_PEA_1_T9 2358 2423 WO 2005/072050 PCT/IB2005/000433 299 Segment cluster Z21368_PEA_1_node_61 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z21368_PEA_1_T1O, Z21368_PEA_1_TI 1, Z21368_PEAlT5, Z21368_PEAIT6 and Z21368_PEA_1_T9. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA-_T10 3168 3201 Z21368_PEA_1_Tl1 3090 3123 Z21368_PEAIT5 2937 2970 Z21368_PEA_1_T6 2937 2970 Z21368_PEAl-T9 2867 2900 10 Segment cluster Z21368_PEA_1_node_68 according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA_1_T1O, Z21368_PEA_1_TI 1 Z21368-PEA_1_T5, Z21368_PEA_1_T6 and Z21368_PEA_1-T9. Table 39 below describes 15 the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1_TIO 4375 4427 Z21368-PEAI_T11 4297 4349 Z21368-PEA_1_T5 4144 4196 Z21368_PEA_1_T6 4144 4196 Z21368_PEA_1_T9 4074 4126 WO 2005/072050 PCT/IB2005/000433 300 Segment cluster Z21368_PEA-_1node_7 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368-PEA_1_T1O, Z21368_PEA__TI 1, 5 Z21368_PEALT23, Z21368_PEA-_IT24, Z21368_PEA_1_T5, Z21368-PEAlT6 and Z21368_PEAlT9. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z21368_PEA_1-T1O 463 557 Z21368_PEA_1_TI1 463 557 Z21368_PEA_1_T23 463 557 Z21368-PEA_1_T24 463 557 Z21368_PEA__T5 301 395 Z21368_PEA_1_T6 301 395 Z21368_PEAl-T9 328 422 10 Overexpression of at least a portion of this cluster was determined according to oligonucleotides and one or more chips. The results were as follows: Oligonucleotide Z21368_0_0_61857 was on the TAA chip and was found to be overexpressed in breast cancer. Variant protein alignment to the previously known protein: 15 Sequence name: /tmp/5ER3vIMKE2/9LOY7lDlTQ:SUL1HUMAN Sequence documentation: Alignment of: Z21368 PEA_1 P2 x SUL1 HUMAN 20 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 301 Quality: 7664.00 Escore: 0 Matching length: 761 Total length: 761 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 11il1lll1l11 11lll 1l 11l1ll 111llll 11lll 111l1lllll llll ll 15 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 I i|||| 1 1||11|||11| | | 1 | 11111111l1111|||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 20 - - 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 |||||||| 11|| | |1 ||||||||||||||||||11 1 11l 111 I 11 I lI 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 25 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 ||I l l i I I 111i111 IlI l111|||| 1|||11|| | 1111|| I||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 30 11 l| i|111|| 11| 11 1||| 11 |11 ||1111|||1 | 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 WO 2005/072050 PCT/IB2005/000433 302 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 Ill l li l l ll l l l l l l l l l l l l l l l l l l l 11 11lll l lll l l l l l l l l l l l 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 5 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 li l l l l l l l l l l l I Ill l l l l l l l l l l l l l l l l11l l l l l l l l l l l l l l l l li1 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 10 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 1 5 l i l l l l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l ll1 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 11||1 |||||||11 1111 1| 11 || 1l l1111 l lll l l 11 11 l11 II 20 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 501 DKECSCRESGYPASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 25 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 30 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 |||1 |1 ||||111 11||1 11 1 ||1 1111111|1l l l ll l ll 1 ll 1ll WO 2005/072050 PCT/IB2005/000433 303 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 i IiI i l I I I Il| |lil I l i 1I I I 1 I I 1l1il 11ill|| 1l111|||||I|| 5 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 11I1||Ill1i1I 11|||I I II l 1111 I I|II Il 11llll1i I | i l Il1 il 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 10 751 NNHWQTAPFWN 761 I III III ||1 751 NNHWQTAPFWN 761 15 20 Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:Q7Z2W2 Sequence documentation: Alignment of: Z21368_PEA_1_P5 x Q7Z2W2 25 Alignment segment 1/1: Quality: 7869.00 Escore: 0 30 Matching length: 791 Total length: 871 WO 2005/072050 PCT/IB2005/000433 304 Matching Percent Similarity: 99.87 Matching Percent Identity: 99.87 Total Percent Similarity: 90.70 Total Percent Identity: 90.70 5 Gaps: 1 Alignment: 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELA. ..-.- .......................................... 58 15 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 59 .... .................................. FFGKYLNEYNGS 70 1111111 ||111 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTVFFGKYLNEYNGS 150 20 - - 71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 25 121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220 30 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSDDSVERLYNML 300 WO 2005/072050 PCT/IB2005/000433 305 221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270 111il ll lllllllllll llll l l lllllllll l 1 1llll1 li1 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 5 271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 10 321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370 IIlIIIIlIIIl IIIIIIIlllll llll ll llllllll1 llll11 llI I 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 421. DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470 20 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 25 521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 30 571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620 | | l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l ll11 1 1 1 1 I WO 2005/072050 PCT/IB2005/000433 306 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670 5 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720 lillllll l l l llllllllllllllI ll lll lll ll ll !l 751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800 10 721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770 II1I 1IIIIIIIIII 111II 11I 111II 1I |llllllllllllllllll 801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850 15 771 GNKDGGSYDLHRGQLWDGWEG 791 851 GNKDGGSYDLHRGQLWDGWEG 871 20 Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:AAH12997 25 Sequence documentation: Alignment of: Z21368_PEA_1_P5 x AAH12997 . 30 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 307 Quality: 420.00 Escore: 0 Matching length: 40 Total length: 40 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 752 LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG 791 15 1 LRSCQGYKQCNPRPKNLDVGNKDGGSYDIHRGQLWDGWEG 40 20 Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:SUL1_HUMAN Sequence documentation: 25 Alignment of: Z21368_PEA_1_P5 x SUL1_HUMAN Alignment segment 1/1: 30 Quality: 7878.00 Escore: 0 WO 2005/072050 PCT/IB2005/000433 308 Matching length: 791 Total length: 871 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 90.82 Total Percent Identity: 90.82 Gaps: 1 Alignment: 10 - - 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 11111111111111111111111111|1111111111lll ll llllllli 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 15 51 DDQDVEL...... ..................................... 57 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 58 .... ................................. AFFGKYLNEYNGS 70 20 1 1 1 1 1 1 1 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120 25 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 30 - - - 171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220 WO 2005/072050 PCT/IB2005/000433 309 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270 5 | | | | | | | | | | | | | | 1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320 10 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 15 371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 20 421 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPDLQASSGGNRGRMLA 520 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570 30 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 WO 2005/072050 PCT/IB2005/000433 310 571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620 1 1 11111111 1 I ilill ll ll i Il l il~ll il I I I |1111111 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 5 621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670 1li illIlilIl illllllllll iII|||| 1111111111111 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720 10 11I|| 751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800 721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770 15 801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850 771 GNKDGGSYDLHRGQLWDGWEG 791 IlI1111111Il I Il11l ll1il 851 GNKDGGSYDLHRGQLWDGWEG 871 20 25 Sequence name: /tmp/AVAZGWHuFO/RzHFOnHIsT:SULlHUMAN Sequence documentation: 30 Alignment of: Z21368_PEA_1_P15 x SULlHUMAN WO 2005/072050 PCT/IB2005/000433 311 Alignment segment 1/1: Quality: 4174.00 Escore: 0 5 Matching length: 416 Total length: 416 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 1 1i l l l l l l l l l 1 ll l l l l l l l l l l l l i l l l l l l l l 11ll l l Illl l l l l l l I 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 25 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 30 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 WO 2005/072050 PCT/IB2005/000433 312 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSV-ERLYML 300 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 10 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 15 401 NKKAKIWRDTFLVERG 416 401 NKKAKIWRDTFLVERG 416 20 25 Sequence name: /tmp/JhwgRdKqmt/kqSmjxkWWk:SULlHUMAN Sequence documentation: Alignment of: Z21368_PEA_1_P16 x SUL1_HUMAN 30 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 313 Quality: 3985.00 Escore: 0 Matching length: 397 Total 5 length: 397 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 10 Gaps: 0 Alignment: 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 20 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 25 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 30 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 1I 11 11Ill1 11l1 1l I l l ll Ill I llllI111 l I11111 11 WO 2005/072050 PCT/IB2005/000433 314 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 1111 I|11 l i i I I|| I I I I I III II IIII 111|| I | | | |11111 5 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 I 1111 111111111 I |I 11111111 I i|||||||| ii|||II|1IIIIIII I I 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 10 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397 i l Iii l I I I 11 1111 1||||1111111111 I I 1 I|| | | 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397 15 20 Sequence name: /tmp/GPlnIw3BOg/zXFdxqG4ow:SULlHUMAN Sequence documentation: Alignment of: Z21368_PEA_1_P22 x SUL1_HUMAN . 25 Alignment segment 1/1: Quality: 1897.00 Escore: 0 30 Matching length: 188 Total length: 188 WO 2005/072050 PCT/IB2005/000433 315 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 10 111 11 I I I I I I I I I I 1l111 I I I I I|||| I I l I I|| I I I I 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 111111 lill I 1 I I 11111ll111 II I 1111 I I I III I 111111 |I I I I I II 15 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 II i1 I II Il l I 1111111||| 11 ||1111 I l1l11111 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 20 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188 i1111 I1111 I 1111I11 I 1111 || ||II lI 111111I11 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188 25 30 Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:Q 7

Z

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2 WO 2005/072050 PCT/IB2005/000433 316 Sequence documentation: Alignment of: Z21368_PEA_1_P23 x Q7Z2W2 5 Alignment segment 1/1: Quality: 1368.00 Escore: 0.000511 Matching length: 137 Total 10 length: 137 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 20 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 11|| 1111 111 1111111111|||II I || 1llll I l lI III 111 25 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 111111111 1111I I I111 1111111 II||| I I l lIII 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 30 WO 2005/072050 PCT/IB2005/000433 317 5 Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:SULlHUMAN Sequence documentation: Alignment of: Z21368_PEA_1_P23 x SUL1_HUMAN 10 Alignment segment 1/1: Quality: 1368.00 Escore: 0.000511 15 Matching length: 137 Total length: 137 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 20 Identity: 100.00 Gaps: 0 Alignment: 25 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 IIillli 11 11 lilllllllllll I llllllll lllllll li iill 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 30 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 WO 2005/072050 PCT/IB2005/000433 318 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 5 Expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368seg39 in normal and cancerous breast tissues 10 Expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by or according to seg39, Z21368seg39 amplicon and Z21368seg39F and Z21368seg39R primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank 15 Accession No. NM_000194; amplicon - HPRTl-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of 20 the normal post-mortem (PM) samples (Sample Nos. 56-60,63-67, Table I above, Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 13 is a histogram showing over expression of the above- indicated SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 transcripts in cancerous breast samples relative 25 to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5-fold over-expression, out of the total number of samples tested is indicated in the bottom. As is evident from Figure 13, the expression of SJL1_HUMAN - Extracellular sulfatase 30 Sulf- 1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue WO 2005/072050 PCT/IB2005/000433 319 samples in testing panel). Notably an over-expression of at least 5 fold was found in 13 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. 5 The P value for the difference in the expression levels of SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.14E-03. Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.91E-03 as checked by exact fisher test. The above values 10 demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: Z21368seg39F forward primer; Z21368seg39R reverse primer. 15 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z21368seg39. Z21368seg39F (SEQ ID NO:842)- GTTGCATTTCTCAGTGCTGGTTT 20 Z21368seg39R (SEQ ID NO:843)- AGGGTGCCGGGTGAGG Z21368seg39 (SEQ ID NO:844) GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGATTGAGTTTCTCTACCATC CTCCCCACGTTCTTCTCTAAGCTGCCTCCAAGCCTCACCCGGCACCCT 25 Expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368seg39 in different normal tissirs Expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by 30 or according to Z21368seg39 amplicon and Z21368seg39F Z21368seg39R was measured by real time PCR. In parallel the expression of four housekeeping genes -[ RPL19 (GenBank WO 2005/072050 PCT/IB2005/000433 320 Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA amplicon) was measured similarly. For each RT sample, the expression of the above amplicon 5 was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (sample nos. 33-35 in table 2 "Tissue samples in normal panel") to obtain a value of relative expression of each sample relative to median of the Normal samples. Primers and amplicon are as above. 10 The results are presented in Figure 14, demonstrating the expression of SUL 1_HUMAN - Extracellular sulfatase Sulf- I Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39, in different normal tissues. 15 Expression of SUL1-HUMAN - Extracellular sulfatase Sulf- 1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368juncl7-21 in normal and cancerous breast tissues Expression of SUL 1-HUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by or according to Z21368junc17-21 amplicon and Z21368juncl7-21F and Z21368juncl7-21R 20 primers was measured by real time PCR. In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above 25 amplicon was normalized to the geometric nean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos 56-60,63-67 Table 1 above, "Tissue samples in testing panel"), o obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. 30 Figure 15 is a histogram showing over expression of the above- indicated SUL 1_HUMAN - Extracellular sulfatase Sulf- 1 transcripts in cancerous breast samples relative WO 2005/072050 PCT/IB2005/000433 321 to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom. 5 As is evident from Figure 15, the expression of SULlHUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in II out of 28 adenocarcinoma samples. 10 Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of SUL _HUMAN - Extracellular sulfatase Sulf- 1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 4.6E-03. 15 Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.78E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non- limiting illustrative example only of a suitable primer pair: 20 Z21368junc1 7-21F forward primer; Z21368junc1 7-21R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: Z21368juncl 7 21 25 Z21368juncl7-21F (SEQ ID NO:845)- GGACGGATACAGCAGGAACG Z21368junc17-21R (SEQ ID NO:846)- TATTTTCCAAAAAAGGCCAGCTC Z21368juncl7-21 (SEQ ID NO:847) GGACGGATACAGCAGGAACGAAAAAACATCCGACCCAACATTATTCTTGTGCTTAC 30 CGATGATCAAGATGTGGAGCTGGCCTTTTTTGGAAAATA WO 2005/072050 PCT/IB2005/000433 322 Expression of SUL1_HUMAN - Extracellular sulfatase Sulf-1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368juncl7-21 in different normal tissues 5 Expression of SUL 1_Hj-UMAN - Extracellular sulfatase Sulf- 1 Z21368 transcripts detectable by or according to amplicon Z21368juncl7-21 was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL19 (GenBank Accession No. NM_000981; RPL 19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA 10 amplicon), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes, as above. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples 15 (Sample Nos. - 33-35 Table 2 above, 'Tissue samples on nonnal panel"), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above. The results are presented in Figure 16, demonstrating the expression of SUL 1_HUMAN 20 - Extracellular sulfatase Sulf-1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368junc17-21, in different normal tissues. DESCRIPTION FOR CLUSTER T59832 25 Cluster T59832 features 6 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No T59832_T1l 103 WO 2005/072050 PCT/IB2005/000433 323 T59832_Ti5 104 T59832_T22 105 T59832_T28 106 T59832 T6 107 T59832_TS 108 Table 2 - Segments of interest Segment Name Sequence ID No T59832_node_1 109 T59832_node_22 110 T59832_node_23 111 T59832_node_24 112 T59832_node_29 113 T59832_node_39 114 T59832_node_7 115 T59832_node_10 116 T59832_node_11 117 T59832_node_12 118 T59832_node_14 119 T59832_node_16 120 T59832_node_19 121 T59832_node_2 122 T59832 node 20 123 T59832_node_25 124 T59832_node_26 125 T59832_node_27 126 T59832_node_28 127 T59832_node_3 128 T59832_node_30 129 WO 2005/072050 PCT/IB2005/000433 324 T59832_node_31 130 T59832_node_32 131 T59832_node_34 132 T59832_node_35 133 T59832_node_36 134 T59832-node_37 135 T59832_node_38 136 T59832_node_4 137 T59832_node_5 138 T59832-node_6 139 T59832_node_8 140 T59832_node_9 141 Table 3 - Proteins of interest Protein Name Sequence ID No i59832P5 143 T59832_P7 144 T59832_P9 145 T59832_P12 146 T59832_P18 147 These sequences are variants of the known protein Gamma- interferon inducible lysosornal 5 thiol reductase precursor (SwissProt accession identifier GILTIHTMAN; known also according to the synonyms Gamma-interferon-inducible protein IP-30), SEQ ID NO: 142, referred to herein as the previously known protein. Protein Gamma- interferon inducible lysosomal thiol reductase precursor is known or believed to have the following function(s): Cleaves disulfide bonds in proteins by reduction. 10 May facilitate the complet unfolding of proteins destined for lysosomal degradation. May be involved in MHIC class II-restricted antigen processing. The sequence for protein Gamma interferon inducible lysosomal thiol reductase precursor is given at the end of the application, as WO 2005/072050 PCT/IB2005/000433 325 "Gamma-interferon inducible lysosomal thiol reductase precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 109 L->S 130 H ->L 5 Protein Gamma- interferon inducible lysosomal thiol reductase precursor localization is believed to be Lysosomal. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: extracellular; lysosome, which are annotation(s) related to Cellular Component. 10 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster T59832 can be used as a diagnostic marker according to overexpression of 15 transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 17 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 17 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma. 25 Table 5 - Normal tissue distribution WO 2005/072050 PCT/IB2005/000433 326 Name of Tissue Number Adrenal 208 Bladder 205 Bone 200 Brain 18 Colon 236 Epithelial 143 General 280 head and neck 192 Kidney 71 Liver 53 Lung 459 lymph nodes 248 Breast 0 bone marrow 94 Ovary 0 Pancreas 20 Prostate 86 Skin 29 Stomach 109 T cells 557 Thyroid 0 Uterus 63 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPi R3 SP2 R4 adrenal 4.9e-01 5.9e-01 4.7e-03 1.1 2.9e-02 0.8 bladder 3.7e-01 5.6e-01 3.7e-02 1.3 2.5e-01 0.9 Bone 6.6e-01 6.7e-01 3.4e-01 0.6 9.le-01 0.4 WO 2005/072050 PCT/IB2005/000433 327 Brain 1.8e-01 2.9e-01 4.3e-03 3.8 2.8e-02 2.5 colon 4.4e-01 5.2e-01 6.le-01 0.9 8.le-01 0.7 epithelial 2.5e-02 1.6e-01 1.2e-05 1.6 9.8e-02 i.1 general 1.3e-02 1.6e-01 1 0.8 1 0.6 Head and neck 3.4e-01 3.3e-01 1 0.4 9.4e-01 0.5 kidney 7.7e-01 8.5e-01 1.4e-01 1.3 4.2e-01 0.9 Liver 8.3e-01 7.6e-01 1 0.5 1 0.6 Lung 5.7e-01 8.3e-01 3.5e-01 0.8 9.8e-01 0.5 lymph nodes 5.7e-01 6.6e-01 7.6e-01 0.8 3.6e-02 1.1 breast 5.0e-02 1.3e-01 2.5e-03 6.5 4.4e-02 3.6 Bone marrow 6.2e-01 7.8e-01 1 0.3 9.5e-01 0.5 ovary 2.2e-01 9.4e-02 3.2e-03 6.1 8.3e-03 5.3 pancreas 9.0e-02 1.6e-02 1.le-03 4.0 7.9e-04 4.2 prostate 8.le-01 8.0e-01 5.7e-01 0.9 4.le-01 0.9 skin 1.6e-01 1.2e-01 2.3e-02 6.0 1.0e-02 2.2 stomach 5.5e-01 7.4e-01 9.4e-01 0.6 4.9e-01 1.0 T cells 1 6.7e-01 6.9e-01 1.0 9.8e-01 0.5 Thyroid 2.3e-01 2.3e-01 5.9e-02 2.5 5.9e-02 2.5 uterus 7.4e-02 4.7e-02 2.2e-02 2.0 6.2e-02 1.7 As noted above, cluster 159832 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Gamma interferon inducible lysosomal thiol reductase precursor. A description of each variant protein according to the present invention is now provided. 5 Variant protein T59832_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T6. An alignment is given to the known protein (Gamma- interferon inducible lysosomal thiol reductase precursor) at the end of the application. One or more alignments to one or more previously published protein 10 sequences are given at the end of the application.

WO 2005/072050 PCT/IB2005/000433 328 Comparison report between T59832_P5 and GILTHUMAN: 1.An isolated chimeric polypeptide encoding for T59832P5, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino 5 acids 12 - 55 of GILTHUMAN, which also corresponds to amino acids 1 - 44 of T59832P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGTRAPRGRCPCRVPGKTLFSSRRCGHTP 10 SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG corresponding to amino acids 45 - 189 of T59832_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832P5, comprising a polypeptide 15 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG in T59832_P5. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 25 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein T59832_P5 is encoded by the following transcript(s): T59832T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript 30 T59832_T6 is shown in bold; this coding portion starts at position 149 and ends at position 715. The transcript also has the following SNPs as listed in Table 7 (given according to their position WO 2005/072050 PCT/IB2005/000433 329 on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 61 C ->T Yes 148 G ->T Yes 1505 G ->C Yes 1651 T-> No 1652 T G Yes 1717 C ->A No 1722 C-> No 1722 C ->G No 1752 A ->G Yes 1S17 A ->G Yes 1854 C-> No 1854 C->A No 212 ->A No 1871 C ->T Yes 1886 T ->G No 1906 G ->A No 1906 G->C No 1942 C -> No 1942 C -> T No 1971 C -> No 1986 G -> A No 2001 G -> T Yes WO 2005/072050 PCT/IB2005/000433 330 2008 A-> No 241 G->T No 2030 -> T No 2031 C->T No 2050 C -> No 2056 A -> G Yes 2068 G -> A Yes 2111 A -> C Yes 2136 A -> C Yes 2144 T->C Yes 244 A -> G Yes 962 C ->T Yes 1074 G ->A Yes 1248 G ->C Yes 1441 G ->A Yes 1443 G->A No Variant protein T59832_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_TS. An alignment is 5 given to the known protein (Gamma- interferon inducible lysosomal thiol reductase precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T59832_P7 and GILTHUMAN: 10 1.An isolated chimeric polypeptide encoding for T59832P7, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM 15 ECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNG corresponding to amino acids 12 WO 2005/072050 PCT/IB2005/000433 331 - 223 of GILTHUMAN, which also corresponds to amino acids I - 212 of T59832_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 5 213 - 238 of T59832P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7. Comparison report between T59832_P7 and BAC98466 (SEQ ID NO:848): I.An isolated chimeric polypeptide encoding for T59832_P7, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLILRGPLKKSNA 15 PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1 - 212 of BAC98466, which also corresponds to amino acids I - 212 of T59832_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 20 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 213 - 238 of T59832_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832P7, comprising a polypeptide 25 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7. Comparison report between T59832_P7 and BAC85622 (SEQ ID NO:849): I .An isolated chimeric polypeptide encoding for T59832P7, comprising a first amino 30 acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having WO 2005/072050 PCT/IB2005/000433 332 the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids 1 - 90 of T59832P7, and a second amino acid sequence being at least 90 % homologous to 5 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1 - 148 of BAC85622, which also corresponds to amino acids 91 - 238 of T598322P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 2.An isolated polypeptide encoding for a head of T59832_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P7. 15 Comparison report between T59832_P7 and Q8WU77 (SEQ ID NO:850): 1.An isolated chimeric polypeptide encoding for T59832P7, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 20 QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1 - 212 of Q8WU77, which also corresponds to amino acids 1 - 212 of T59832P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 25 the sequence VRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 213 - 238 of T59832P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 30 at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR in T59832_P7.

WO 2005/072050 PCT/IB2005/000433 333 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide. Variant protein T59832_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is 10 known or not; the presence of known SNPs in variant protein T59832P7 sequence provides support for the deduced sequere of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 146 I-> No 146 I ->M Yes 168 P->Q No 170 L -> No 170 L->V No 180 M -> V Yes 76 R->Q Yes 77 A->T No Variant protein T59832_P7 is encoded by the following transcript(s): T59832T8, for 15 which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T8 is shown in bold; this coding portion starts at position 149 and ends at position 862. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P7 WO 2005/072050 PCT/IB2005/000433 334 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 61 C -> T Yes 148 G -> T Yes 651 C->A No 656 C-> No 656 C ->G No 686 A ->G Yes 751 A ->G Yes 1004 T-> G Yes 1206 C -> No 1206 C ->A No 1223 C ->T Yes 1238 T-> G No 212 -> A No 1258 G->A No 1258 G->C No 1294 C-> No 1294 C->T No 1323 C-> No 1338 G ->A No 1353 G ->T Yes 1360 A-> No 1382 -> T No 1383 C->T No 241 G->T No WO 2005/072050 PCT/IB2005/000433 335 1402 C -> No 1408 A->G Yes 1420 G->A Yes 1463 A->C Yes 1488 A->C Yes 1496 T->C Yes 244 A->G Yes 375 G->A Yes 377 G->A No 439 G -> C Yes 585 T-> No 586 T->G Yes Variant protein T59832_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T 11. An alignment 5 is given to the known protein (Gamma- interferon inducible lysosomal thiol reductase precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T59832_P9 and GILTHUMAN: I.An isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 15 QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 12 - 214 of GILT_HUMAN, which also corresponds to amino acids 1 - 203 of T59832_P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having WO 2005/072050 PCT/IB2005/000433 336 the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to amino acids 204 - 244 of T59832P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832 P9, comprising a polypeptide 5 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. Comparison report between T59832_P9 and BAC98466 (SEQ ID NO:848): 1.An isolated chimeric polypeptide encoding for T59832_P9, comprising a first amino 10 acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids I - 203 of 15 BAC98466, which also corresponds to amino acids 1 - 203 of T59832 P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to amino acids 204 - 244 of T59832-P9, wherein said first and second amino acid sequences are 20 contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. 25 Comparison report between T59832_P9 and BAC85622: 1.An isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids I - 90 of WO 2005/072050 PCT/IB2005/000433 337 T59832 P9. second amino acid sequence being at least 90 % homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1 - 113 of BAC85622, which also corresponds to amino acids 91 5 203 of T59832_P9, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to amino acids 204 - 244 of T59832P9, wherein said first, second and third amino acid sequences are 10 contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of T59832_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA 15 PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P9. 3.An isolated polypeptide encoding for a tail of T59832P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKLRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. 20 Comparison report between T59832_P9 and Q8WT77 (SEQ ID NO:850): I.An isolated chimeric polypeptide encoding for T59832P9, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 25 QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1 - 203 of Q8WU77, which also corresponds to amino acids I - 203 of T59832P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 30 the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR corresponding to WO 2005/072050 PCT/IB2005/000433 338 amino acids 204 - 244 of T59832P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T59832_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 5 at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR in T59832_P9. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T59832_P9 also has the following non-silent SNPs (Single Nucleotide 15 Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations SNP positions) on amino acid Alterative amino acid(s) Previously known SNP? sequence 146 I-> No 146 I-> M Yes 222 A->P No 222 A -> T No 234 P -> No 234 P->S No 243 G -> No 76 R-> Q Yes 77 A -> T No WO 2005/072050 PCT/IB2005/000433 339 168 P->Q No 170 L-> No 170 L->V No 180 M->V Yes 204 N -> No 204 N ->K No 210 P->L Yes 215 L->W No Variant protein T59832_P9 is encoded by the following transcript(s): T59832T1 1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_TI1 is shown in bold; this coding portion starts at position 149 and ends at position 5 880. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 61 C -> T Yes 148 G->T Yes 651 C -> A No 656 C -> No 656 C -> G No 686 A -> G Yes 751 A -> G Yes 760 C -> No 760 C -> A No 777 C -> T Yes WO 2005/072050 PCT/IB2005/000433 340 792 T-> G No 812 G->A No 212 -> A No 812 G->C No 848 C-> No 848 C->T No 877 C -> No 892 G->A No 907 G->T Yes 914 A -> No 936 -> T No 937 C -> T No 956 C -> No 241 G->T No 962 A->G Yes 974 G->A Yes 1017 A->C Yes 1042 A->C Yes 1050 T->C Yes 244 A -> G Yes 375 G -> A Yes 377 G->A No 439 G->C Yes 585 T-> No 586 T->G Yes Variant protein T59832_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_TI5. An 5 alignment is given to the known protein (Gamma- interferon inducible lysosomal thiol reductase WO 2005/072050 PCT/IB2005/000433 341 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between T59832_P12 and GILTHUMAN: 1.An isolated chimeric polypeptide encoding for T59832P12, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVP TAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC 10 QHGEEECKFNKVE corresponding to amino acids 12 - 141 of GILTHUMAN, which also corresponds to amino acids 1 - 130 of T59832_P12, and a second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173 - 261 of 15 GILTHUMAN, which also corresponds to amino acids 131 - 219 of T59832_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T59832P12, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 20 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between T59832_P12 and BAC85622: 25 1.An isolated chimeric polypeptide encoding for T59832P12, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPNYKTGNLYLRGPLKKSNA 30 PLVNVTLYYEALCGGCRAFLIRELFPTWLLV corresponding to amino acids 1 - 90 of T59832_P12, second amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 342 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids I - 40 of BAC85622, which also corresponds to amino acids 91 - 130 of T59832_P12, third amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTBIECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG 5 corresponding to amino acids 72 - 122 of BAC85622, which also corresponds to amino acids 131 - 181 of T59832P12, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 182 10 - 219 of T59832P12, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of T59832_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 15 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P12. 3.An isolated chimeric polypeptide encoding for an edge portion of T59832P12, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 20 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. 4.An isolated polypeptide encoding for a tail of T59832P12, comprising a polypeptide 25 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK in T59832_P12. Comparison report between T59832_P12 and Q8WU77: 1.An isolated chimeric polypeptide encoding for T59832P12, comprising a first amino 30 acid sequence being at least 90 % homologous to

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA

WO 2005/072050 PCT/IB2005/000433 343 PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1 - 130 of Q8WU77, which also corresponds to amino acids 1 - 130 of T59832_P12, and a second amino acid sequence being at least 90 % homologous to 5 CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of Q8WU77, which also corresponds to amino acids 131 - 219 of T59832P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T59832P12, 10 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and 15 ending at any of amino acid numbers 131+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 20 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein T59832_P12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is 25 known or not; the presence of known SNPs in variant protein T59832P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 137 P->Q No WO 2005/072050 PCT/IB2005/000433 344 139 L-> No 76 R->Q Yes 77 A->T No 139 L->V No 149 M->V Yes 183 P -> No 183 P->T No 200 G->A No 200 G->D No 212 S -> No 212 S->F No Variant protein T59832_P12 is encoded by the following transcript(s): T59832Ti5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T15 is shown in bold; this coding portion starts at position 149 and ends at position 5 805. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 13 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 61 C -> T Yes 148 G -> T Yes 563 C -> G No 593 A -> G Yes 658 A -> G Yes 695 C -> No 695 C->A No WO 2005/072050 PCT/IB2005/000433 345 712 C->T Yes 727 T -- >G No 747 G->A No 747 G ->C No 783 C-> No 212 -> A No 783 C->T No 812 C-> No 827 G->A No 842 G->T Yes 849 A -> No 871 ->T No 872 C -> T No 891 C -> No 897 A -> G Yes 909 G -> A Yes 241 G->T No 952 A -> C Yes 977 A->C Yes 985 T->C Yes 244 A -> G Yes 375 G -> A Yes 377 G->A No 439 G-> C Yes 558 C->A No 563 C -> No Variant protein T59832_P18 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T22. An WO 2005/072050 PCT/IB2005/000433 346 alignment is given to the known protein (Gamma- interferon inducible lysosomal thiol reductase precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein 5 is as follows: Comparison report between T59832_P18 and GILTHJUMAN: 1.An isolated chimeric polypeptide encoding for T59832P18, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino 10 acids 12 - 55 of GILT_HUMAN, which also corresponds to amino acids 1 - 44 of T59832_P18, and a second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173 - 261 of GILTHUMAN, which also corresponds to amino acids 45 - 133 of T59832_P18, wherein said 15 first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T59832P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 20 least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between T59832_P18 and Q8WLT77: 1.An isolated chimeric polypeptide encoding for T59832_P18, comprising a first amino 25 acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1 - 44 of QSWU77, which also corresponds to amino acids 1 - 44 of T59832P18, and a second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED 30 QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of WO 2005/072050 PCT/IB2005/000433 347 Q8WU77, which also corresponds to amino acids 45 - 133 of T59832_P18, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of T59832P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in 5 length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+ ((n-2) - x), in which x varies from 0 to n-2. 10 Comparison report between T59832_P18 and Q8NEI4 (SEQ ID NO:851): 1.An isolated chimeric polypeptide encoding for T59832P18, comprising a first amino acid sequence being at least 90 % homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1 - 44 of Q8NEI4, which also corresponds to amino acids I - 44 of T59832P18, and a 15 second amino acid sequence being at least 90 % homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162 - 250 of Q8NEI4, which also corresponds to amino acids 45 - 133 of T59832P 18, wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 2.An isolated chimeric polypeptide encoding for an edge portion of T59832P 18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a 25 structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 30 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072050 PCT/IB2005/000433 348 prediction programs predict that this protein' has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein T59832_P18 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid 5 sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 114 G ->A No 114 G ->D No 126 S-> No 126 S ->F No 51 P->Q No 53 L-> No 53 L-> V No 63 M -> V Yes 97 P-> No 97 P->T No 10 Variant protein T59832_P18 is encoded by the following transcript(s): T59832T22, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T22 is shown in bold; this coding portion starts at position 149 and ends at position 547. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column 15 indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 349 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 61 C ->T Yes 148 G ->T Yes 437 C-> No 437 C ->A No 454 C ->T Yes 469 T->G No 489 G -> A No 489 G -> C No 525 C-> No 525 C ->T No 554 C-> No 569 G ->A No 212 -> A No 584 G -> T Yes 591 A-> No 613 -> T No 614 C -> T No 633 C-> No 639 A -> G Yes 651 G->A Yes 694 A -> C Yes 719 A -> C Yes 727 T->C Yes 241 G ->T No 244 A ->G Yes 300 C ->A No 305 C-> No 305 C -> G No WO 2005/072050 PCT/IB2005/000433 350 335 A -> G Yes 400 A-> G Yes As noted above, cluster T59832 features 33 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster T59832 node_1 according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11, T59832-T15, T59832_T22, T59832_T6 and 10 T59832_TS. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-TIl 1 123 T59832Ti5 1 123 T59832_T22 1 123 T59832_T6 1 123 T59832TS 1 123 15 Segment cluster T59832_node_22 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T28 1 523 20 WO 2005/072050 PCT/IB2005/000433 351 Segment cluster T59832_node_23 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28. Table IS below describes the starting and 5 ending position of this segment on each transcript. Table IS - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832 T28 524 652 Segment cluster T59832-node_24 according to the present invention is supported by 4 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T28 653 901 15 Segment cluster T59832_node_29 according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28 and T59832_TS. Table 20 below describes the starting and ending position of this segment on each transcript. 20 Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T28 1055 1472 T59832_T8 785 1202 WO 2005/072050 PCT/IB2005/000433 352 Segment cluster T59832_node_39 according to the present invention is supported by 195 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_TI 1, T59832-T15, T59832jT22, T59832_T28, T59832_T6 and T59832T8. Table 21 below describes the starting and ending position of this 5 segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 1031 1084 T59832_Ti5 966 1019 T59832_T22 708 761 T59832_T28 1747 1800 T59832 T6 2125 2178 T59832_T8 1477 1530 Segment cluster T59832_node_7 according to the present invention is supported by 8 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832T6. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832 T6 281 1346 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 20 WO 2005/072050 PCT/IB2005/000433 353 Segment cluster T59832_node_10 according to the present invention is supported by 332 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832TI 1, T59832_T15, T59832_T6 and T59832-TS. Table 23 below describes the starting and ending position of this segment on each transcript 5 Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 338 382 T59832_T15 338 382 T59832_T6 1404 1448 T59832_TS 338 382 Segment cluster T59832_node_ 11 according to the present invention is supported by 306 libraries. The number of libraries was determined as previously described. This segment can be 10 found in the following transcript(s): T59832_TI 1, T59832_T15, T59832_T6 and T59832_T8. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-Til 383 417 T59832_T15 383 417 T59832_T6 1449 1483 T59832_T8 383 417 15 Segment cluster T59832_node_12 according to the present invention is supported by 280 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T598321 1, T59832_T15, T59832_T6 and T59832_TS. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 354 Transcript name Segment starting position Segment ending position T59832_Tll 418 463 T59832_T15 418 463 T59832_T6 1484 1529 T59832_T8 418 463 Segment cluster T59832_node_14 according to the present invention is supported by 280 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T5 9832 T 11, T59832T5, T59832_T6 and T59832_T8. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 464 502 T59832T15 464 502 T59832_T6 1530 1568 159832_18 464 502 10 Segment cluster T59832_node_16 according to the present invention is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11, T59832T 15, T59832_T6 and T59832_T8. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T11 503 538 T59832_T15 503 538 T59832_T6 1569 1604 T59832 T8 503 538 WO 2005/072050 PCT/IB2005/000433 355 Segment cluster T59832_node_19 according to the present invention is supported by 300 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T59832_T 1I, T59832_T6 and T59832_TS. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-T1l 539 577 T59832_T6 1605 1643 T59832_TS 539 577 10 Segment cluster T59832_node-2 according to the present invention is supported by 258 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_TI1, T59832_TI5, T59832_T22, T59832_T6 and T59832_TS. Table 29 below describes the starting and ending position of this segment on each transcript. 15 Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-Tll 124 154 T59832_TI5 124 154 T59832_T22 124 154 T59832_T6 124 154 T59832_TS 124 154 Segment cluster T59832_node-20 according to the present invention is supported by 318 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072050 PCT/IB2005/000433 356 found in the following transcript(s): T59832_TI 1, T59832_T6 and T59832_T8. Table 30 below describes the starting and ending position of this segment on each tran'script. Table 30 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tl1 578 631 T59832_T6 1644 1697 T59832-T8 578 631 5 Segment cluster T59832-node_25 according to the present invention can be found in the following transcript(s): T59832T1 1, T59832_TI5, T59832_T22, T59832_T28, T59832_T6 and T59832_TS. Table 31 below describes the starting and ending position of this segment on each transcript. 10 Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 632 653 T59832_TI5 539 560 T59832_T22 281 302 T59832_T2S 902 923 T59832_T6 1698 1719 632 653 Segment cluster T59832_node_26 according to the present invention is supported by 342 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): T59832_T11, T59832_T15, T59832_T22, T59832_T2S, T59832_T6 and T59832_TS. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 357 Transcript name Segment starting position Segment ending position T59832-Tll 654 717 T59832T15 561 624 T59832_T22 303 366 T59832-T28 924 987 T59832_T6 1720 1783 T59832_TS 654 717 Segment cluster T59832_node 27 according to the present invention is supported by 314 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T59832_T11, T59832_T15, T59832_T22, T59832_T28, T59832_T6 and T59832_TS. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T11 718 756 T59832 T15 625 663 T59832_T22 367 405 T59832_T28 988 1026 T59832_T6 1784 1822 159832_18 718 756 10 Segment cluster T59832_node-28 according to the present invention is supported by 284 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832T15, T59832T22, T59832_T28, T59832_T6 and T59832_T8. Table 34 below describes the starting and ending position of this segment on each 15 transcript.

WO 2005/072050 PCT/IB2005/000433 358 Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_TI5 664 691 T59832_T22 406 433 T59832_T28 1027 1054 T59832_T6 1823 1850 T59832_T8 757 784 Segment cluster T59832_node_3 according to the present invention can be found in the 5 following transcript(s): T59832TI 1, T59832_T15, T59832_T22, T59832_T6 and T59832_TS. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T1 155 172 T59832_Ti5 155 172 159832_T22 155 172 T59832_T6 155 172 T59832_T8 155 172 10 Segment cluster T59832_node_30 according to the present invention can be found in the following transcript(s): T59832_111, T59832jT15, T59832T22, T59832_T28, T59832_T6 and T59832_18. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T11 757 760 159832T15 692 695 WO 2005/072050 PCT/IB2005/000433 359 T59832_T22 434 437 T59832_T28 1473 1476 T59832_T6 1851 1854 T59832_T8 1203 1206 Segment cluster T59832_node_31 according to the present invention can be found in the following transcript(s): T59832_TI 1, T59832_T15, T59832_T22, T59832T28, T59832T6 5 and T59832_T8. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 761 780 T59832_T5 696 715 T59832_T22 438 457 T59832_T28 1477 1496 T59832_T6 1855 1874 159832 18 1207 1226 10 Segment cluster 159832_node932 according to the present invetion is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): 159832_111, 159832115, T59832T..22, 159832_128, 159832_16 and 159832_18. Table 38 below describes the starting and ending position of this segment on each transcript. 15 Table 38 - Segmnent location on transcr-ipts Transcript name Segment starting position Segment ending position 15983-2 117 781 810 T59832_T85 716 745 WO 2005/072050 PCT/IB2005/000433 360 T59832_T22 458 487 T59832 T28 1497 1526 T59832_T6 1875 1904 T59832_T8 1227 1256 Segment cluster T59832_node_34 according to the present invention can be found in the following transcript(s): T59832_TI1, T59832_T15, T59832_T22, T59832T28, T59832_T6 5 and T59832_T8. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tl 811 832 T59832T15 746 767 T59832_T22 488 509 T59832_T28 1527 1548 T59832_T6 1905 1926 T59832 T8 1257 1278 10 Segment cluster T59832_node_35 according to the present invention can be found in the following transcript(s): T59832_T11, T59832_15, T59832T22, T59832_T28, T59832_T6 and T59832-T8. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tl 833 836 T59832 T15 768 771 T59832_T22 510 513 WO 2005/072050 PCT/IB2005/000433 361 T59832_T28 1549 1552 T59832_T6 1927 1930 T59832_T8 1279 1282 Segment cluster T59832_node_36 according to the present invention can be found in the following transcript(s): T59832Tll , T59832_TI5, T59832T22, T59832_T28, T59832-T6 5 and T59832-T8. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment starting position Segment ending position. T59832_Tll 837 845 T59832_TI5 772 780 T59832_T22 514 522 T59832_T28 1553 1561 T59832_T6 1931 1939 T59832_T8 1283 1291 10 Segment cluster T59832_node_37 according to the present invention is supported by 300 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_TI1, T59832_T5, T59832_T22, T59832_T28, T59832_T6 and T59832_T8. Table 42 below describes the starting and ending position of this segment on each transcript. 15 Table 42 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 846 945 T59832_Ti5 781 880 T59832_T22 523 622 WO 2005/072050 PCT/IB2005/000433 362 T59832_T28 1562 1661 T59832_T6 1940 2039 T59832_T8 1292 1391 Segment cluster T59832_node_38 according to the present invention is supported by 247 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T59832_T 11, T59832_T15, T59832_T22, T59832_T28, T59832_T6 and T59832_T8. Table 43 below describes the starting and ending position of this segment on each transcript. Table 43 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-Tll 946 1030 T59832T15 881 965 T59832T22 623 707 T59832_T28 1662 1746 T59832_T6 2040 2124 T59832_T8 1392 1476 10 Segment cluster T59832_node_4 according to the present invention is supported by 296 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832T1 1, T59832_T15, T59832_T22, T59832_T6 and T59832_T8. Table 44 below describes the starting and ending position of this segment on each 15 transcript. Table 44 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_T11 173 223 T59832T15 173 223 WO 2005/072050 PCT/IB2005/000433 363 T59832_T22 173 223 T59832_T6 173 223 T59832_T8 173 223 Segment cluster T59832-node_5 according to the present invention is supported by 305 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): T59832_Til, T59832_T15, T59832_T22, T59832_T6 and T59832_T8. Table 45 below describes the starting and ending position of this segment on each transcript. Table 45 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 224 259 T59832_TI5 224 259 T59832_T22 224 259 T59832_T6 224 259 T59832_T8 224 259 10 Segment cluster T59832_node_6 according to the present invention can be found in the following transcript(s): T59832_T11, T59832_T15, T59832T22, T59832_T6 and T59832_T8. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832_Tll 260 280 T59832_TI5 260 280 T59832_T22 260 280 T59832_T6 260 280 T59832_T8 260 280 WO 2005/072050 PCT/IB2005/000433 364 Segment cluster T59832_node_8 according to the present invention can be found in the following transcript(s): T59832T 11, T59832_T15, T59832_T6 and T59832_T8. Table 47 5 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-Til 281 301 T59832_TI5 281 301 T59832_T6 1347 1367 T59832_T8 281 301 Segment cluster T59832_node-9 according to the present invention is supported by 330 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_TI1, T59832_T15, T59832_T6 and T59832_T8. Table 48 below describes the starting and ending position of this segment on each transcript. Table 48 - Segment location on transcripts Transcript name Segment starting position Segment ending position T59832-T11 302 337 T59832_T15 302 337 T59832_T6 1368 1403 T59832_T8 302 337 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/YQPBtaxsLQ/JxSZR3ZR2p:GILTHUMAN WO 2005/072050 PCT/IB2005/000433 365 Sequence documentation: Alignment of: T59832_P5 x GILTHUMAN 5 Alignment segment 1/1: Quality: 429.00 Escore: 0 10 Matching length: 46 Total length: 46 Matching Percent Similarity: 97.83 Matching Percent Identity: 97.83 Total Percent Similarity: 97.83 Total Percent 15 Identity: 97.83 Gaps: 0 Alignment: 20 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKVG 46 12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTG 57 25 Sequence name: /tmp/9HrQ57oZGO/ugNVzp0l7X:GILT HUMAN 30 Sequence documentation: WO 2005/072050 PCT/IB2005/000433 366 Alignment of: T59832_P7 x GILTHUMAN Alignment segment 1/1: 5 Quality: 2110.00 Escore: 0 Matching length: 212 Total length: 212 10 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 l l l l l l l l l l l l l l l l l ll l l l l l l l l l l l l l I1 1| | | | | | 1 1 1 1 1 1 | | 20 12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 I I I1 1l l l l l l l l l l l l l l l l l l l l l l l1 1 1l l l l l l l1 l l l1 l lI i l l l ii 62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111 25 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 I 1 1 I l l l l l l l I l l l l l l l l l I l l l l l l l l l l l l l l l l l l l l l l lI 112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161 30 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 l1 1i l ll l l l l l l l l l l l l l l l l l l l l l l l l l l l 1 Ill l l l l l l l l l l l l l lI WO 2005/072050 PCT/IB2005/000433 367 162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211 201 PHEYVPWVTVNG 212 | | | | | | | | | | 1 1 5 212 PHEYVPWVTVNG 223 10 Sequence name: /tmp/9HrQ57oZG0/ugNVzp0l7X:BAC98466 Sequence documentation: 15 Alignment of: T59832_P7 x BAC98466 Alignment segment 1/1: 20 Quality: 2110.00 Escore: 0 Matching length: 212 Total length: 212 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072050 PCT/IB2005/000433 368 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 il I~ll l I|||1111l1l|11|1|1llll11lllil1 ill111 I||||||| 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 5 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 il il lllll lllll I 1ll1 11111111|||1 Il1i il l il | 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 10 Il l lI I11 I ll1i1 I 1l i 1l 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 l 111l ill11ll ll1 111111||lIIIIIIIlllIIII I|||Ill11ll I| 15 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 201 PHEYVPWVTVNG 212 201 PHEYVPWVTVNG 212 20 25 Sequence name: /tmp/9HrQ57oZGO/ugNVzpO17X:BACB56 2 2 Sequence documentation: 30 Alignment of: T59832_P7 x BAC85622

.

WO 2005/072050 PCT/IB2005/000433 369 Alignment segment 1/1: Quality: 1496.00 Escore: 0 5 Matching length: 148 Total length: 148 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 140 1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50 141 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 190 2 0 i l l l l l i l l l l l l l l l l l l l l l l l l l l l l l l l l 1 l l l l l l l l l l l l l lI 51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100 191 NAQRTDALQPPHEYVPWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR 238 25 101 NAQRTDALQPPHEYVPWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR 148 30 WO 2005/072050 PCT/IB2005/000433 370 Sequence name: /tmp/9HrQ57oZGO/ugNVzpOl7X:Q8WU 77 Sequence documentation: 5 Alignment of: T59832_P7 x Q8WU77 Alignment segment 1/1: Quality: 2110.00 10 Escore: 0 Matching length: 212 Total length: 212 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 - - 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 11illllllilll 1lllll 1l 111ll 11lll 1ll 1ll 1l 1 llll llll ll 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 25 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 l i l l l l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l Il l l l I l l i 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 30 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 WO 2005/072050 PCT/IB2005/000433 371 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 I I il i l li l 1I 111 I I II 1I 1 I i I i Il l I i | l I 11111||||||||| 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 5 201 PHEYVPWVTVNG 212 I II I l l I | | 201 PHEYVPWVTVNG 212 10 15 Sequence name: /tmp/lttCiW300d/feIXLDs4rU:GILTHUMAN Sequence documentation: Alignment of: T59832_P9 x GILTHUMAN 20 Alignment segment 1/1: Quality: 2016.00 Escore: 0 25 Matching length: 203 Total length: 203 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 30 Identity: 100.00 Gaps: 0 WO 2005/072050 PCT/IB2005/000433 372 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 5 12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 Ilii l ii|| 1||||l l 11||||| 1 I| | |I 111 I I 1 |||||11111 || 10 62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 li|i 11 I I| 1 ||1 1 1 | 1 1 ||1 I 1 ||||11 t I Il l I I|Il l I 112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161 15 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 I1l11111 ll | Il 1111 i I 1||||I1 I 1| | |1 ||||11 I111111 162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211 20 201 PHE 203 ||| 212 PHE 214 25 Sequence name: /tmp/lttCiW300d/feIXLDs4rU:BAC98466 30 Sequence documentation: WO 2005/072050 PCT/IB2005/000433 373 Alignment of: T59832_P9 x BAC98466 Alignment segment 1/1: 5 Quality: 2016.00 Escore: 0 Matching length: 203 Total length: 203 10 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps~: 0 15 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 20 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 25 - - 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 30 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 1 WO 2005/072050 PCT/IB2005/000433 374 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 201 PHE 203 III 5 201 PHE 203 10 Sequence name: /tmp/lttCiW30od/feIXLDs4rU:BAC85622 Sequence documentation: 15 Alignment of: T59832_P9 x BAC85622 Alignment segment 1/1: 20 Quality: 1145.00 Escore: 0 Matching length: 113 Total length: 113 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072050 PCT/IB2005/000433 375 91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 140 |1 Il1ll1 lll1 ll11 l1i11 Il l i l i ||||||||||||||||||1 I I | 1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50 5 141 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 190 51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100 191 NAQRTDALQPPHE 203 10 | | | | | 1 | | 101 NAQRTDALQPPHE 113 15 Sequence name: /tmp/lttCiW30od/feIXLDs4rU:Q8WU77 20 Sequence documentation: Alignment of: T59832_P9 x QBWU77 Alignment segment 1/1: 25 Quality: 2016.00 Escore: 0 Matching length: 203 Total length: 203 30 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 376 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 I lill 11ll l l 1llll ll 11ll lllll l ll llll lllll llll ll llllll|11 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 10 - - 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 1illlllllll11 l1 lll1 l1 lll1l1 llll1 111 ||ii1|| |1 ||||1 I 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 15 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKV5ACVLDELDMELAFLTIVCME 150 ||1 |||||1 ||||||! 1 ||1 111111 |1 |||ii l l1 ll1 ll lll1 ll 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 201||| |1|||1 1 1 1 ||1 1 || 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 201 PHE 203 III 25 201 PHE 203 30 WO 2005/072050 PCT/IB2005/000433 377 Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc:GILT_HUMAN Sequence documentation: 5 Alignment of: T59832_P12 x GILTHUMAN Alignment segment 1/1: Quality: 2084.00 10 Escore: 0 Matching length: 219 Total length: 250 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 87.60 Total Percent Identity: 87.60 Gaps: 1 Alignment: 20 - - 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 1illl1 l1 lll1 l11 ll111 l1 ll11 llll1 |||1 ||11 11|1 ||I 1111 12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61 25 51 RGPLKKSNAPLVNVTLYYEALCGGCPAFLIRELFPTWLLVMEILNVTLVP 100 11i l l 1ll l l 11l l l l l l 11ll l l l l l l l 11ll l l l l l l ll l l l l lll l l l 62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVE ....................... 130 30 |||| 1 | 11 1 ||111 11 112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161 WO 2005/072050 PCT/IB2005/000433 378 131 ............ CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 169 I I 111| ||| I11111111i 1 1 I I| | | | 111111 I|| 162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211 5 - 170 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 219 I II i iii 111I| 1|1 lIilIIII 11 1 1 1 11 I 1|111I|||II ili||l||| 212 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 261 10 15 Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc:BAC85622 Sequence documentation: Alignment of: T59832_P12 x BAC85622 20 Alignment segment 1/1: Quality: 835.00 Escore: 0 25 Matching length: 91 Total length: 122 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 74.59 Total Percent 30 Identity: 74.59 Gaps: 1 WO 2005/072050 PCT/IB2005/000433 379 Alignment: 91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE .......... .130 5 1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50 131 ....................... CLQLYAPGLSPDTIMECAMGDRGMQLMHA 159 10 51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100 160 NAQRTDALQPPHEYVPWVTVNG 181 101 NAQRTDALQPPHEYVPWVTVNG 122 15 20 Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc : Q8WU77 Sequence documentation: 25 Alignment of: T59832_P12 x Q8WU77 Alignment segment 1/1: Quality: 2084.00 30 Escore: 0 WO 2005/072050 PCT/IB2005/000433 380 Matching length: 219 Total length: 250 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 87.60 Total Percent Identity: 87.60 Gaps: 1 Alignment: 10

-

1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 15 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVE ....................... 130 2 0 I l i l l i l l l l l l l l l l l l l l l l l l l l l l i 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 131 ........... .CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 169 | | 1 1 1 1 1 1 | | | 1 1 1 1 1 | | | 1 1 1 1 | 1 l l l l li 25 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 170 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 219 201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250 30 WO 2005/072050 PCT/IB2005/000433 381 5 Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:GILTHUMAN Sequence documentation: Alignment of: T59832_P18 x GILTHUMAN 10 Alignment segment 1/1: Quality: 1222.00 Escore: 0 15 Matching length: 133 Total length: 250 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 53.20 Total Percent 20 Identity: 53.20 Gaps: 1 Alignment: 25 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK ...... 44 12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61 44 ...................................................... 44 30 62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111 WO 2005/072050 PCT/IB2005/000433 382 44 ...... .................................................. 44 112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161 5 45 ............ CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83 162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211 10 84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133 lilllllllllllllllllllllllllllll1l1lll1lllllllliil 212 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 261 15 Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:Q8WU77 20 Sequence documentation: Alignment of: T59832_P18 x Q8WU77 25 Alignment segment 1/1: Quality: 1222.00 Escore: 0 Matching length: 133 Total 30 length: 250 WO 2005/072050 PCT/IB2005/000433 383 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 53.20 Total Percent Identity: 53.20 5 Gaps: 1 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK ...... 44 10 111l 11llllllllllll11l 1llllI lll11 l1 llll I llllllllI II 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 44........................................................ 44 15 51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100 44........................................................ 44 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 20 - - 45 ............ CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 25 84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133 201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250 30 WO 2005/072050 PCT/IB2005/000433 384 Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:Q8NEI4 5 Sequence documentation: Alignment of: T59832_P18 x Q8NEI4 Alignment segment 1/1: 10 Quality: 1222.00 Escore: 0 Matching length: 133 Total length: 250 15 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 53.20 Total Percent Identity: 53.20 Gaps: 1 20 Alignment: 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK. ...... 44 111ll 11l1 Illlllllll11l11lll 1lll 11lll lll lll IllII 25 1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50 ........................................................ 44 51 RGPLKKSNAPLVNVTLYYEALCGGCQAFLIRELFPTWLLVMEILNVTLVP 100 30 44....................................... 44 WO 2005/072050 PCT/IB2005/000433 385 101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150 45 ............ CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83 5 | | || || || | 151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200 84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133 10 201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250 Expression of gamma-interferon inducible lysosomal thiol reductase (GILT) T59832 transcripts 15 which are detectable by amplicon as depicted in sequence name T59832junc6-25-26 in normal and cancerous breast tissues Expression of gamma-interferon inducible lysosomal thiol reductase (GILT) transcripts detectable by or according to junc6-25-26, T59832junc6-25-26 amplicon and primers T59832junc6-25-26F T59832junc6-25-26R was measured by real time PCR. In parallel the 20 expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1 amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the 25 quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1 above, "Tissue samples in testing panel", above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 18 is a histogram showing over expression of the above-indicated gamma 30 interferon inducible lysosomal thiol reductase (GILT) transcripts in cancerous breast samples relative to the normal samples.

WO 2005/072050 PCT/IB2005/000433 386 As is evident from Figure 18, the expression of gamma- interferon inducible lysosomal thiol reductase (GILT) transcripts detectable by the above amplicon(s) in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1 above, "Tissue samples in testing panel"). Notably an over-expression of at least 7 fold was 5 found in 3 out of 28 adenocarcinoma samples. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: T59832junc6-25-26F forward primer; and T59832junc6-25-26R reverse primer. 10 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: T59832junc6 25-26. Forward primer T59832junc6-25-26F (SEQ ID NO :852): 15 CCACCAGTTAACTACAAGTGCCTG Reverse primer T59832junc6-25-26R (SEQ ID NO :853): GCGTGCATGAGCTGCATG Amplicon T59832junc6-25-26 (SEQ ID NO :854): CCACCAGTTAACTACAAGTGCCTGCAGCTCTACGCCCCAGGGCTGTCGCCAGACAC TATCATGGAGTGTGCAATGGGGGACCGCGGCATGCAGCTCATGCACGC 20 DESCRIPTION FOR CLUSTER I-IUMGRP5E Cluster HU MGRP5E features 2 transcript(s) and 5 segment(s) of interest, the names for 25 which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. HUMGRP5E T4 148 HUMGRP5E T5 149 WO 2005/072050 PCT/IB2005/000433 387 Table 2 - Segments of interest Segment Name Sequence ID No. HUMGRP5E node 0 150 HUMGRP5E node 2 151 HUMGRP5E node_8 152 HUMGRP5E node 3 153 HUfJMGRP5E node 7 154 Table 3 - Proteins of interest Protein Name Sequence ID No. HUMGRP5EP4 156 HUJMGRP5EP5 157 5 These sequences are variants of the known protein Gastrin-releasing peptide precursor (SwissProt accession identifier GRP-HUMAN; known also according to the synonyms GRP; GRP-10), SEQ ID NO: 155, referred to herein as the previously known protein. Gastrin-releasing peptide is known or believed to have the following function(s): 10 stimulates gastrin release as well as other gastrointestinal hormones. The sequence for protein Gastrin-releasing peptide precursor is given at the end of the application, as "Gastrin-releasing peptide precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 4 S -> R 15 Protein Gastrin-releasing peptide localization is believed to be Secreted.

WO 2005/072050 PCT/IB2005/000433 388 The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Diabetes, Type II. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential 5 pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Bombesin antagonist; Insulinotropin agonist. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: 10 Anorectic/Antiobesity; Releasing hormone; Anticancer; Respiratory; Antidiabetic. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; neuropeptide signaling pathway, which are annotation(s) related to Biological Process; growth factor, which are annotation(s) related to Molecular Function; and secreted, which are annotation(s) related to Cellular Component. 15 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. As noted above, cluster HUMGRP5E features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Gastrin-releasing 20 peptide precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMGRP5EP4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGRP5ET4. 25 An alignment is given to the known protein (Gastrin-releasing peptide precursor) at the end of the application One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 30 Comparison report between HUMGRP5EP4 and GRPHUMAN: WO 2005/072050 PCT/IB2005/000433 389 1.An isolated chimeric polypeptide encoding for HUMGRP5EP4, comprising a first amino acid sequence being at least 90 % homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNIHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED 5 SSNFKDVGSKGK corresponding to amino acids 1 - 127 of GRPHUMAN, which also corresponds to amino acids 1 - 127 of HUMGRP5EP4, and a second amino acid sequence being at least 90 % homologous to GSQREGRNPQLNQQ corresponding to amino acids 135 148 of GRPHUMAN, which also corresponds to amino acids 128 - 141 of HUJMGRP5EP4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 2.An isolated chimeric polypeptide encoding for an edge portion of HUMGRP5E_P4, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KG, having a 15 structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128 + ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein HrUMGRP5EP4 also has the following non-silent SNPs (Single 25 Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5EP4 sequence provides support for the deduced seqnce of this variant protein according to the present invention). 30 Table 5 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 390 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 4 S->R Yes Variant protein HUMGRP5E_P4 is encoded by the following transcript(s): HLUMGRP5ET4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGRP5ET4 is shown in bold; this coding portion starts at 5 position 622 and ends at position 1044. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5EP4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 6 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 541 ->T No 542 G ->T No 631 A ->C Yes 672 G ->A Yes 1340 C-> No 1340 C->A No 1341 A-> No 1341 A ->G No Variant protein HUIGRP5EP5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGRP5ET5. 15 An alignment is given to the known protein (Gastrin-releasing peptide precursor) at the end of the application. One or more alignments to one or more previously published protein sequences WO 2005/072050 PCT/IB2005/000433 391 are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMGRP5E_P5 and GRP_HUMAN: 5 1.An isolated chimeric polypeptide encoding for HUMGRP5E_P5, comprising a first amino acid sequence being at least 90 % homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1 - 127 of GRP-HUMAN, which also 10 corresponds to amino acids 1 - 127 of HUMGRP5E_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DSLLQVLNVKEGTPS corresponding to amino acids 128 - 142 of HUMGRP5EP5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of HUMGRP5E_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS in HUMGRP5E_P5. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 25 region prediction program predicts that this protein has a trans- membrane region. Variant protein HUMGRP5E_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5E_P5 30 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072050 PCT/IB2005/000433 392 Table 7 - Anino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 4 S -> R Yes Variant protein HUMGRP5EP5 is encoded by the following transcript(s): HUMGRP5ET5, for which the sequence(s) is/are given at the end of the application. The 5 coding portion of transcript HUJMGRP5ET5 is shown in bold; this coding portion starts at position 622 and ends at position 1047. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUR1MGRP5EP5 sequence provides support for the deduced 10 sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 541 -> T No 542 G->T No 631 A ->C Yes 672 G ->A Yes 1354 C-> No 1354 C->A No 1355 A-> No 1355 A->G No As noted above, cluster E-UMGRP5E features 5 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are 15 of particular interest. A description of each segment according to the present invention is now provided.

WO 2005/072050 PCT/IB2005/000433 393 Segment cluster HUMGRP5E-node_0 according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGRP5ET4 and HIUMGRP5ET5. Table 9 below describes the starting and ending position of this segment on each transcript. 5 Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position HU-JMGRP5ET4 1 760 HUIMGRP5ET5 1 760 Segment cluster FTMGRP5E-node_2 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can 10 be found in the following transcript(s): HUMGRP5ET4 and HJMGRP5ET5. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGRP5ET4 761 984 HUMGRP5ET5 761 984 15 Segment cluster HUMGRP5E_node_S according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H[UMGRP5ET4 and HUMGRP5ET5. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGRP5ET4 1004 1362 HTMGRP5ET5 1018 1376 20 WO 2005/072050 PCT/IB2005/000433 394 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are 5 included in a separate description. Segment cluster HUMGRP5E-node_3 according to the present invention can be found in the following transcript(s): HUMGRP5ET4 and HIUJMGRP5ET5. Table 12 below describes the starting and ending position of this segment on each transcript. 10 Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGRP5ET4 985 1003 HUMGRP5ET5 985 1003 Segment cluster HUMGRP5Enode_7 according to the present invention can be found in the following transcript(s): HUMGRP5ET5. Table 13 below describes the starting and ending 15 position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position HIUMGRP5ET5 1004 1017 Variant protein alignment to the previously known protein: 20 Sequence name: /tmp/412zs2mwyT/BOwjOUAXOd:GRPHUMAN Sequence documentation: Alignment of: HUMGRP5EP4 x GRPHUMAN WO 2005/072050 PCT/IB2005/000433 395 Alignment segment 1/1: Quality: 1291.00 5 Escore: 0 Matching length: 141 Total length: 148 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 95.27 Total Percent Identity: 95.27 Gaps: 1 Alignment: 15 . 1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50 ||||| 1 1 11 I 1||1 ||1| || |1 | l ll l l l l l l l1l l1 l II 1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50 20 51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100 | | | | | || | I 1| 1 | | | | 1 1| |1|| | 1 1|1 | | | || |1 | | | || || |||1 51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100 101 PKALGNQQPSWDSEDSSNFKDVGSKGK....... .GSQREGRNPQLNQQ 141 25 | I| 1 1 | | | | | |I111111 1111111| 101 PKALGNQQPSWDSEDSSNFKDVGSKGKVGRLSAPGSQREGRNPQLNQQ 148 30 WO 2005/072050 PCT/IB2005/000433 396 Sequence name: /tmp/lme9ldnvfv/KbP5ioBPtU:GRPHUMAN Sequence documentation: 5 Alignment of: HUMGRP5E_P5 x GRPHUMAN Alignment segment 1/1: 10 Quality: 1248.00 Escore: 0 Matching length: 127 Total length: 127 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50 1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50 25 - - - 51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100 51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100 30 101 PKALGNQQPSWDSEDSSNFKDVGSKGK 127 l i l l l l I ll l l l l l l l l l l l l l l l l liI WO 2005/072050 PCT/IB2005/000433 397 101 PKALGNQQPSWDSEDSSNFKDVGSKGK 127 5 Expression of GRPHUMAN - gastrin-releasing peptide(HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7 in normal and cancerous breast tissues. 10 Expression of GRPHUMAN - gastrin-releasing peptide transcripts detectable by or according to junc3-7, HUMGRP5Ejunc3-7 amplicon(s) and HUMGRP5Ejunc3-7F and HUMGRP5Ejunc3-7R primers was measured by real time PCR. In parallel the expression of 15 four housekeeping genes PBGD (GenBank Accession No. BC019323; amplicon - PBGD amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRTl-amplicon), and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quartities of the. 20 housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 19 is a histogram showing over expression of the above- indicated GRP-HUMAN 25 - gastrin- releasing peptide transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. As is evident from Figure 19, the expression of GRP_HUMAN - gastrin-releasing peptide transcripts detectable by the above amplicon(s) in cancer samples was significantly 30 higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1 "Tissue samples WO 2005/072050 PCT/IB2005/000433 398 in testing panel"). Notably an over-expression of at least 5 fold was found in 12 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. 5 The P value for the difference in the expression levels of GRP_HUMAN - gastrin releasing peptide transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 7.22E-04. Threshold of 5 fold over expression was found to differentiate between cancer and normal samples with P value of 1. 12F02 as checked by exact fisher test. The above values 10 demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: HUMGRP5Ejunc3-7F forward primer; and HUMGRP5Ejunc3-7R reverse priiner. 15 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: HUMGRP5Ejunc3-7. HUMGRP5Ejunc3-7F (SEQ ID NO:855) 20 ACCAGCCACCTCAACCCA HUMGRP5Ejunc3-7R (SEQ ID NO:856) CTGGAGCAGAGAGTCTTTGCCT HUMGRP5Ejunc3-7 (SEQ ID NO:857) ACCAGCCACCTCAACCCAAGGCCCTGGGCAATCAGCAGCCTTCGTGGGATTCAGAG 25 GATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTCTCTGCTCCAG Expression of GRP._HUMAN - gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7 in different normal tissues. 30 Expression of GRPHUMAN - gastrin-releasing peptide transcripts detectable by or according to HUMGRP5E junc3-7 amplicon(s) and HUMGRP5E junc3-7F and HUMGRP5E WO 2005/072050 PCT/IB2005/000433 399 junc3-7R was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL 19 (GenBank Accession No. NM_000981; RPL 19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon 5 SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos. 33-35 above, Table 2, "Tissue samples in normal panel"), to obtain a value of relative expression of each sample relative to median of the breast samples. 10 Primers and amplicon are as above. The results are presented in Figure 20, demonstrating the expression of GRPHUMAN gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7, in different normal tissues. 15 DESCRIPTION FOR CLUSTER AA155578 Cluster AA155578 features 4 transcript(s) and 15 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 20 Table ] - Transcripts of interest Transcript Name Sequence ID No. AA155578_PEA1_T1O 158 AA155578_PEA 1 T12 159 AA155578_PEA1_T13 160 AA155578_PEA 1 T8 161 Table 2 - Segments of interest Segment Name Sequence ID No. AA 155578-PEA_1_node 11 162 WO 2005/072050 PCT/IB2005/000433 400 AA155578 _PEA_1_node_12 163 AA1555;78_PEA_Inode_14 164 AA155578_PEAI_node_19 165 AA155578_PEA_1 node_21 166 AA155578-PEA_1_node_23 167 AA155578-PEA_1_node_24 168 AA155578_PEA-_1node_25 169 AA155578_PEA_1_node_4 170 AA155578_PEA-_1node_7 171 AA155578-PEA_1_node_15 172 AA155578_PEA-1.node-18 173 AA155578_PEA I node_22 174 AA155578_PEA1node 6 175 AA155578_PEA_1_node_8 176 Table 3 - Proteins of interest Protein Name Sequence ID No. AA155578_PEA_1_P4 178 AA155578_PEA_1_P6 179 AA155578-PEA_1_PS 180 AA155578_PEA_1_P9 181 These sequences are variants of the known protein Kallikrein 10 precursor (SwissProt 5 accession identifier KLKAHUMAN; known also according to the synonyms EC 3.4.21.-; Protease serine- like 1; Normal epithelial cell-specific 1), SEQ ID NO: 177, referred to herein as the previously known protein. Protein Kallikrein 10 precursor is known or believed to have the following function(s): Has a tumor-suppressor role for NESI in breast and prostate cancer. The sequence for protein 10 Kallikrein 10 precursor is given at the end of the application, as "Kallikrein 10 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4.

WO 2005/072050 PCT/IB2005/000433 401 Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 50 A->S 149 P->L Protein Kallikrein 10 precursor localization is believed to be Secreted (Probable). The following GO Annotation(s) apply to the previously known protein. The following 5 annotation(s) vere found: proteolysis and peptidolysis, which are annotation(s) related to Biological Process; chymotrypsin; trypsin; serine-type peptidase; hydrolase, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl 10 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster AA155578 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 15 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 21 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 21 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. 25 Table 5 - Normal tissue distribution Name of Tissue Number WO 2005/072050 PCT/IB2005/000433 402 Brain 0 Colon 0 epithelial 17 general 5 head and neck 0 Lung 14 Ovary 0 pancreas 0 prostate 4 Skin 80 stomach 0 Uterus 45 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 Brain 1 3.7e-01 1 1.0 3.5e-02 5.1 Colon 6.3e-02 2.9e-02 2.4e-01 2.9 1.6e-01 3.2 epithelial 4.9e-03 2.0e-02 7.5e-04 2.1 2.3e-03 1.9 general 7.8e-07 7.2e-06 3.8e-10 4.8 2.6e-10 4.4 head and neck 1.0e-02 3.5e-02 4.6e-01 2.5 7.5e-01 1.4 Lung 8.5e-0I 9.2e-01 1 0.5 1 0.5 Ovary 2.2e-01 1.6e-01 1.0e-02 3.3 1.8e-02 3.4 pancreas 3.3e-01 6.9e-02 3.2e-02 3.7 2.4e-04 10.0 prostate S.3e-01 8.7e-01 6.7e-01 1.2 7.5e-01 1.1 Skin 6.0e-01 8.le-01 3.2e-01 1.9 1 0.3 stomach 3.0e-0l 2.7e-01 2.5e-01 3.0 1.6e-01 2.3 Uterus 1.8e-01 3.2e-01 5.6e-01 0.8 6.8e-01 0.8 As noted above, cluster AA155578 features 4 transcript(s), which were listed in Table I above. These transcript(s) encode for protein(s) which are variant(s) of protein Kallikrein 10 WO 2005/072050 PCT/IB2005/000433 403 precursor. A description of each variant protein according to the present invention is now provided. Variant protein AA155578_PEA_1_P4 according to the present invention has an amino 5 acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578-PEA_1_T1O. An alignment is given to the known protein (Kallikrein 10 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as 10 follows: Comparison report between AA155578_PEA_1-P4 and KLKAHUMAN: 1.An isolated chimeric polypeptide encoding for AA155578_PEA_1-P4, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ 15 PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTT RSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP corresponding to amino acids 1 - 146 of KLKAHJMAN, which also corresponds to amino acids 1 - 146 of AA155578_PEA_1_P4, and a second amino acid sequence being at least 90 % homologous to YNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGIL 20 SWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 184 - 276 of KLKA-HUMAN, which also corresponds to amino acids 147 - 239 of AA155578_PEA_1_P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of 25 AA155578_PEA_1_P4, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PY, having a structure as follows: a sequence starting from any of amino acid numbers 30 146-x to 146; and ending at any of amino acid numbers 147+ ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072050 PCT/IB2005/000433 404 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein AA155578_PEA_1_P4 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 123 Q -> R No 145 R-> G No 145 R->M Yes 168 Y -> No 19 K -> No 194 G -> No 43 L->S No 50 A -> S Yes 60 Q ->R No 15 Variant protein AA155578_PEA_1_P4 is encoded by the following transcript(s): AA155578PEA_1_T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA_1_T1O is shown in bold; this coding portion starts at position 148 and ends at position 864. The transcript also has the following SNPs as WO 2005/072050 PCT/IB2005/000433 405 listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 19 C ->G Yes 88 G-> No 570 A -> G Yes 580 A->G No 581 G ->T Yes 651 C-> No 729 C-> No 733 C ->T No 875 G->A No 906 C -> A No 907 C -> A No 952 C -> A No 204 G-> No 953 C -> A No 994 C -> A Yes 1125 C -> T Yes 1192 C -> T Yes 1330 G-> No 1330 G -> T Yes 275 T-> C No 295 G -> T Yes 326 A -> G No WO 2005/072050 PCT/IB2005/000433 406 444 C ->T Yes 465 C ->A Yes 483 G->C Yes 515 A->G No Variant protein AA155578-PEA-1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 AA155578-PEA_1-T12. An alignment is given to the known protein (Kallikrein 10 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between AA155578_PEA_1_P6 and KLKAHUMAN: 1.An isolated chimeric polypeptide encoding for AA155578-PEA-1_P6, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1 - 29 of KLKAHUMAN, which also corresponds to amino acids 1 - 29 of AA155578_PEA_1_P6, and 15 a second amino acid sequence being at least 90 % homologous to VKYNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 182 276 of KLKAHUMAN, which also corresponds to amino acids 30 - 124 of AA155578_PEAlP6, wherein said first and second amino acid sequences are contiguous and 20 in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA_-lP6, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and 25 most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise WV, having a structure as follows: a sequence starting from any of amino acid WO 2005/072050 PCT/IB2005/000433 407 numbers 29-x to 29; and ending at any of amino acid numbers 30+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein AA155578_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 9 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 19 K-> No 53 Y-> No 79 G-> No Variant protein AA155578_PEA_1_P6 is encoded by the following transcript(s): AA155578_PEA_1_T12, for which the sequence(s) is/are given at the end of the application. 20 The coding portion of transcript AA155578_PEA_1_T12 is shown in bold; this coding portion starts at position 148 and ends at position 519. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA_1_P6 sequence provides support 25 for the deduced sequence of this variant protein according to the present invention).

WO 2005/072050 PCT/IB2005/000433 408 Table 10 - Nucleic acid SNPs SNP position on nucleotide 'JUternative nucleic acid Previously known SNP? sequence 19 C -> G Yes 88 G-> No 608 C ->A No 649 C->A Yes 780 C ->T Yes 847 C ->T Yes 985 G-> No 985 G->T Yes 204 G -> No 306 C-> No 384 C-> No 388 C->T No 530 G->A No 561 C -> A No 562 C->A No 607 C -> A No Variant protein AA155578_PEA_1_P8 according to the present invention has an amino 5 acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578_PEA_1_T8. An alignment is given to the known protein (Kallikrein 10 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between AA155578_PEA_1_PS and KLKAHUMAN: 1.An isolated chimeric polypeptide encoding for AA155578-PEA_1_P8, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 409 MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1 - 29 of KLKAHUMAN, which also corresponds to amino acids 1 - 29 of AA155578PEA_1LP8, and a second amino acid sequence being at least 7 0 %, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 5 polypeptide having the sequence GHCGLE corresponding to amino acids 30 - 35 of AA155578_PEAL_PS, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of AA155578_PEA_1_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GHCGLE in AA155578_PEA_1_P8. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein AA155578-PEA_1_PS also has the following non-silent SNPs (Single 20 Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA_1_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). 25 Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 19 K-> No WO 2005/072050 PCT/IB2005/000433 410 Variant protein AA155578_PEA_1-PS is encoded by the following transcript(s): AA155578_PEALT8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA_1_T8 is shown in bold; this coding portion starts at position 285 and ends at position 389. The transcript also has the following SNPs as listed in 5 Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEAlP8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide. Alternative nucleic acid Previously known SNP? sequence 341 G- No 400 C -> T Yes 718 C-> No 796 C-> No 800 C -> T No 942 G ->A No 973 C ->A No 974 C ->A No 1019 C ->A No 1020 C ->A No 1061 C ->A Yes 1192 C ->T Yes 421 C ->A Yes 1259 C ->T Yes 1397 G-> No 1397 G ->T Yes 439 G -> C Yes 471 A ->G No 526 A ->G Yes WO 2005/072050 PCT/IB2005/000433 411 536 A->G No 537 G->T Yes 549 C -> T Yes 587 T-> C No Variant protein AA155578_PEA-1_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 AA155578_PEA_1-T13. An alignment is given to the known protein (Kallikrein 10 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between AA155578_PEAl-P9 and KLKA-HUMAN: 1.An isolated chimeric polypeptide encoding for AA155578_PEAlP9, comprising a first amino acid sequence being at least 90 % homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK corresponding to amino acids 1 - 90 of 15 KLKAHUMAN, which also corresponds to amino acids 1 - 90 of AA155578_PEA_1_P9. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 20 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein AA155578_PEA_1_P9 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the 25 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA-1_P9 WO 2005/072050 PCT/IB2005/000433 412 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 19 K-> No 43 L->S No 50 A ->S Yes 60 Q->R No 5 Variant protein AA155578_PEA_1_P9 is encoded by the following transcript(s): AA155578_PEA_1LTl3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA_1-T13 is shown in bold; this coding portion starts at position 148 and ends at position 417. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the 10 alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA-_P9 sequence provides support for the deduced sequence of this variart protein according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 19 C ->G Yes 88 G-> No 204 G-> No 275 T->C No 295 G -> T Yes 326 A -> G No 559 G -> C Yes 560 C -> G Yes WO 2005/072050 PCT/IB2005/000433 413 582 A-> G Yes 919 T->A Yes As noted above, cluster AA155578 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster AA155578_PEA_1-node_11 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_T1O and 10 AA155578_PEA_1_T13. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578-PEA_TIO 236 416 AA155578_PEA-_1T13 236 416 15 Segment cluster AA155578_PEA-1_node_12 according to tle present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_T13. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segnient starting position Segment ending position AA155578_PEA_1-T13 417 935 20 Segment cluster AA155578_PEA_1_node_14 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 414 segment can be found in the following transcript(s): AA155578_PEA_1_TI0 and AA155578_PEA_1_TS. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578-PEA_1_TI 417 585 AA155578_PEA-1_T8 373 541 5 Segment cluster AA155578-PEA_1_node_19 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_T10, 10 AA155578_PEA_1_T12 and AA155578_PEA_1_T8. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_TI0 586 714 AA155578_PEA_1_T12 241 369 AA155578_PEA_1_T8 653 781 15 Segment cluster AA155578_PEA 1 node_21 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA-1_TI0, AA155578_PEA_1-T12 and AA155578-PEAl_T8. Table 19 below describes the starting and ending position of this segment on each transcript. 20 Table 19 - Segment location on transcripts Transcript name. Segment starting position Segment ending position AA155578PEA-1_TI0 715 863 WO 2005/072050 PCT/IB2005/000433 415 AA155578_PEA_1_T12 370 518 AA155578_PEA_1_TS 782 930 Segment cluster AA155578-PEA_1_node_23 according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): AA155578_PEA-1_T10, AA155578_PEA_1-T12 and AA155578_PEA_1_T8. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_TI0 887 1063 AA155578_PEA1_T12 542 718 AA155578_PEA_1_T8 954 1130 10 Segment cluster AA155578_PEA_1_node_24 according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_TI0, AA155578_PEA_1_T12 and AA155578_PEA_1_T8. Table 21 below describes the starting and 15 ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA-1_TIO 1064 1184 AA155578_PEA1 _T12 719 839 AA155578_PEA_1_T8 1131 1251 Segment cluster AA155578_PEA1_node_25 according to the present invention is 20 supported by 53 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 416 segment can be found in the following transcript(s): AA155578_PEAlLT1O, AA155578_PEA_1-T12 and AA155578_PEA_1_TS. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA-_1T1O 1185 1397 AA155578_PEA-_1T12 840 1052 AA155578_PEA_1_T8 1252 1464 5 Segment cluster AA155578_PEAInode_4 according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578PEALT1O, 10 AA155578_PEA_1_T12 and AA155578_PEA_1-T13. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_T10 1 138 AA155578_PEA_1_T12 1 138 AA155578_PEA._-T13 1 138 15 Segment cluster AA155578_PEA-_Inode_7 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_T8. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578-PEA_1_T8 92 275 WO 2005/072050 PCT/IB2005/000433 417 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster AA155578_PEA_1_node-15 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This 10 segment can be found in the following transcript(s): AA155578_PEA_1_T8. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_T8 542 647 15 Segment cluster AA155578_PEA_1_node_18 according to the present invention can be found in the following transcript(s): AA155578_PEA_1_T12 and AA155578_PEAI_T8. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_T12 236 240 AA155578_PEA_1_T8 648 652 20 Segment cluster AA155578_PEA_1_node-22 according to the present invention can be found in the following transcript(s): AA155578_PEA_1_T10, AA155578_PEA_1_T12 and AA155578_PEAIT8. Table 27 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 418 Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA-1_T1O 864 886 AA155578_PEA_1 T12 519 541 AA155578_PEA_1_T8 931 953 Segment cluster AA155578_PEA_1_node_6 according to the present invention is 5 supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA_1_T8. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA_1_T8 1 91 10 Segment cluster AA155578_PEA_1_node-8 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578-PEA_1_T1O, AA155578_PEA_1_TI2, AA155578_PEA_1-T13 and AA155578_PEA_1_T8. Table 29 below 15 describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position AA155578_PEA-_ T1O 139 235 AA155578_PEA_1_T12 139 235 AA155578_PEA_-T13 139 235 AA155578_PEA_1_T8 276 372 WO 2005/072050 PCT/IB2005/000433 419 Variant protein alignment to the previously known protein: Sequence name: /tmp/4gXdRVOClz/cQ4LqHmh5A:KLKA_HUMAN 5 Sequence documentation: Alignment of: AA155578_PEA_1_P4 x KLKAHUMAN 10 Alignment segment 1/1: Quality: 2283.00 Escore: 0 Matching length: 239 Total 15 length: 276 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 86.59 Total Percent Identity: 86.59 20 Gaps: 1 Alignment: 1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50 25 1 ||1|1||1 ||1|1 ||| |III 1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50 51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100 30l1 lilll li l l llllllll L II l lDQI lll|1111| || || 11 1 30 51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100 WO 2005/072050 PCT/IB2005/000433 420 101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP .... 146 | 1 1| |1 |111|||||| ii ||| iii 1|| 1 |1 ||111 |1 ||||| 101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARPVVPG 150 5 147 ..................................... YNKGLTCSSITILSPKE 163 151 PRVRALQLPYRCAQPGDQCQVAGWGTTAARRVKYNKGLTCSSITILSPKE 200 164 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 213 1 0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | I | I | | | | | | | | | 201 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 250 214 GSAQHPAVYTQICKYMSWINKVIRSN 239 15 251 GSAQHPAVYTQICKYMSWINKVIRSN 276 20 Sequence name: /tmp/3VxcRS97HN/X9ncdxjYQx:KLKA HUMAN Sequence documentation: 25 Alignment of: AA155578_PEA_1_P6 x KLKAHUMAN Alignment segment 1/1: 30 Quality: 1140.00 Escore: 0 WO 2005/072050 PCT/IB2005/000433 421 Matching length: 124 Total length: 276 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 44.93 Total Percent Identity: 44.93 Gaps: 1 Alignment: 10 1 MRAPHLHLSAASGARALAKLLPLLMAQLW. ....................... 29 1 MRAPHLHLSAASGAPALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50 15 29 .............................................. 29 51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100 29 ...-........................................ .... ........... 29 20 101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARPVVPG 150 30 ................................... VKYNKGLTCSSITILSPKE 48 25 151 PRVRALQLPYRCAQPGDQCQVAGWGTTAARRVKYNKGLTCSSITILSPKE 200 49 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 98 201 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 250 30 99 GSAQHPAVYTQICKYMSWINKVIRSN 124 WO 2005/072050 PCT/IB2005/000433 422 251 GSAQHPAVYTQICKYMSWINKVIRSN 276 5 Sequence name: /tmp/LsSdTeuOqX/61uiCMKTi9 : KLKAHUMAN 10 Sequence documentation: Alignment of: AA155578 PEA 1 PB x KLKAHUMAN 15 Alignment segment 1/1: Quality: 279.00 Escore: 0 Matching length: 29 Total 20 length: 29 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 25 Gaps: 0 Alignment: 1 MRAPHLHLSAASGARALAKLLPLLMAQLW 29 30 |1|1 1 |||||||||| 1 MRAPHLHLSAASGARALAKLLPLLMAQLW 29 WO 2005/072050 PCT/IB2005/000433 423 5 Sequence name: /tmp/kcfKGMcF7s/YnKnMy8Dlq:KLKAHUMAN Sequence documentation: 10 Alignment of: AA155578_PEA_1_P9 x KLKAHUMAN Alignment segment 1/1: 15 Quality: 887.00 Escore: 0 Matching length: 90 Total length: 90 Matching Percent Similarity: 100.00 Matching Percent 20 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MPAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50 1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50 30 - 51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK 90 WO 2005/072050 PCT/IB2005/000433 424 51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK 90 DESCRIPTION FOR CLUSTER HSENA78 5 Cluster HSENA78 features 1 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. HSENA78T5 182 10 Table 2 - Segnents of interest Segment Name Sequence ID No. HSENA78_node_0 183 HSENA78_node_2 184 HSENA78_node_6 185 HSENA78_node_9 186 HSENA78_node_3 187 HSENA78_node_4 188 HSENA78_node_8 189 Table 3 - Proteins of interest Protein Name Sequence ID No, HSENA78_P2 191 These sequences are variants of the known protein Small inducible cytokine B5 precursor 15 (SwissProt accession identifier SZ05_HTMAN; known also according to the synonyms CXCL5; Epithelial-derived neutrophil activating protein 78; Neutrophil-activating peptide ENA- 78), SEQ ID NO: 190, referred to herein as the previously known protein.

WO 2005/072050 PCT/IB2005/000433 425 Protein Small inducible cytokine B5 precursor is known or believed to have the following functionss: Involved in neutrophil activation. The sequence for protein Small inducible cytokine B5 precursor is given at the end of the application, as "Small inducible cytokine B5 precursor amino acid sequence". Protein Small inducible cytokine B5 precursor localization is 5 believed to be Secreted. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling; positive control of cell proliferation, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function. 10 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HSENA78 can be used as a diagnostic marker according to overexpression of 15 transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 22 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 22 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and lung malignant tumors. 25 Table 4 - Normal tissue distribution Name of Tissue Number Colon 0 epithelial 2 general 38 kidney 0 WO 2005/072050 PCT/IB2005/000433 426 Lung 3 Breast 8 Skin 0 stomach 36 Uterus 4 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPi R3 SP2 R4 colon 2.6e-01 3.3e-01 1.7e-01 2.7 2.7e-01 2.2 epithelial 2.5e-01 9.0e-02 3.2e-03 4.1 8.5e-07 5.5 general 8.4e-01 7.2e-01 1 0.3 1 0.4 kidney 1 7.2e-01 1 1.0 1.7e-01 1.9 lung 8.5e-01 4.8e-01 4.le-01 1.9 4.0e-05 3.8 breast 9.5e-01 8.7e-01 1 0.8 6.8e-01 1.2 skin 2.9e-01 4.7e-01 1.4e-01 7.0 6.4e-01 1.6 stomach 5.0e-01 4.3e-01 7.5e-01 1.0 4.3e-01 1.3 uterus 7.le-01 8.5e-01 6.6e-O1 1.3 8.0e-01 1.0 As noted above, cluster HSENA78 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible 5 cytokine B5 precursor. A description of each variant protein according to the present invention is now provided. Variant protein HSENA78_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSENA78_T5. An 10 alignment is given to the known protein (Small inducible cytokine B5 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSENA78_P2 and SZ05_HUMAN: WO 2005/072050 PCT/IB2005/000433 427 1.An isolated chimeric polypeptide encoding for HSENA78_P2, comprising a first amino acid sequence being at least 90 % homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1 - 81 of SZ05_HUMAN, 5 which also corresponds to amino acids 1 - 81 of HSENA78_P2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 10 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSENA78_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid 15 sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSENA78_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 80 V- No 81 V-> No 20 Variant protein HSENA78_P2 is encoded by the following transcript(s): HSENA78-T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSENA78_T5 is shown in bold; this coding portion starts at position 149 and ends at position 391. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column 25 indicates whether the SNP is known or not; the presence of known SNPs in variant protein WO 2005/072050 PCT/IB2005/000433 428 HSENA78_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 92 C -> T Yes 144 C -> T No 1151 A -> T Yes 1389 T->C No 1867 C -> G Yes 145 C -> T No 181 C -> T Yes 316 G ->A Yes 388 G No 390 T-> No 605 T-> No 972 C -> T Yes 1105 A -> G Yes 5 As noted above, cluster HSENA78 features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are 10 of particular interest. A description of each segment according to the present invention is now provided. Segment cluster HSENA78_node_0 according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072050 PCT/IB2005/000433 429 found in the following transcript(s): HSENA78_T5. Table 8 below describes the starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 1 257 5 Segment cluster HSENA78_node_2 according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 9 below describes the starting and ending position of this segment on each transcript. 10 Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 258 390 Segment cluster HSENA78_node_6 according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): HSENA78_T5. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 585 2370 20 Segment cluster HSENA78_node_9 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 11 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 430 Table 11 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 2394 2546 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster HSENA78_node_3 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78-T5. Table 12 below describes the starting and ending position of this segment on each transcript. 10 Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position,, HSENA78_T5 391 500 Segment cluster HSENA78_node_4 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): HSENA78_T5. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 501 584 20 Segment cluster HSENA78_node_8 according to the present invention can be found in the following transcript(s): HSENA78_T5. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 431 Transcript name Segment starting position Segment ending position HSENA78_T5 2371 2393 Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially 5 expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 15. Table 15 - Oligonucleotides related to this gene Oligonucleotide name Overexpressed in cancers Chip reference HSENA78_0_1_0 breast cancer Breast 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/5kiQY6MxWx/pLnTrxsCqk:SZ05 HUMAN Sequence documentation: 15 Alignment of: HSENA78_P2 x SZ05_HUMAN Alignment segment 1/1: Quality: 767.00 20 Escore: 0 Matching length: 81 Total length: 81 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 4 32 Gaps: 0 Alignment: 5 1 MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50 1 MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50 51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81 51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81 DESCRIPTION FOR CLUSTER T94936 15 Cluster T94936 features 2 transcript(s) and 12 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. T94936_PEA_1_TI 192 T94936_PEA_1_T2 193 20 Table 2 - Segments of interest Segment Name Sequence I) No. T94936_PEA_1_node_14 194 T94936_PEA_1_node_16 195 T94936_PEA_1_node_2 196 T94936_PEA_1_node_20 197 T94936_PEA_1_node_23 198 WO 2005/072050 PCT/IB2005/000433 433 T94936_PEA-_1node_0 199 T94936_PEA_ 1 node 11 200 T94936_PEA_1-node_13 201 T94936_PEAInode_17 202 T94936_PEA_1_node_6 203 T94936_PEA_1_node_8 204 T94936_PEA_1_node_9 205 Table 3 - Proteins of interest Protein Name Sequence ID No. T94936_PEA-_1P2 206 T94936_PEA__P3 207 As noted above, cluster T94936 features 2 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. 5 Variant protein T94936_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T94936_PEAl_Ti. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 10 variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T94936_PEA_1_P2 and Q8TD06 (SEQ ID NO:858): 1.An isolated chimeric polypeptide encoding for T94936_PEAlP2, comprising a first amino acid sequence being at least 90 % homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS 15 KKPLMVIHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL corresponding to amino acids 1 - 150 of Q8TD06, which also corresponds to amino acids 1 - 150 of T94936_PEA-1_P2. The location of the variant protein was determined according to results from a number of 20 different software programs and analyses, including analyses from SignalP and other specialized WO 2005/072050 PCT/IB2005/000433 434 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 5 Variant protein T94936_PEA_1_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 4, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA_1_P2 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 4 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence, 104 T -> A No 28 K -> R No Variant protein T94936_PEA_1_P2 is encoded by the following transcript(s): T94936-PEA_1_Ti, for which the sequence(s) is/are given at the end of the application. The 15 coding portion of transcript T94936_PEAI_Ti is shown in bold; this coding portion starts at position 76 and ends at position 525. The transcript also has the following SNPs as listed in Table 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA_1_P2 sequence provides support for the deduced 20 sequence of this variant protein according to the present invention). Table 5 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 158 A ->G No 186 A ->G No WO 2005/072050 PCT/IB2005/000433 435 385 A->G No Variant protein T94936_PEA-1_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T94936_PEA_1_T2. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T94936_PEA_1_P3 and QSTD06: 1.An isolated chimeric polypeptide encoding for T94936_PEA_1_P3, comprising a first 10 amino acid sequence being at least 90 % homologous to MMLHSALGLCLLLVTVSSNLAIAHKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFV corresponding to amino acids 1 - 122 of Q8TD06, which also corresponds to amino acids 1 - 122 of T94936_PEAlP3, and a second amino acid sequence being at least 70%, 15 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMYVISFHQIYKISRNQHSCFYF corresponding to amino acids 123 - 145 of T94936-PEA_1-P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of T94936_PEA-lP3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMYVISFHQIYKISRNQHSCFYF in T94936-PEA_1_P3. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane 30 region prediction program predicts that this protein has a trans-membrane region.

WO 2005/072050 PCT/IB2005/000433 436 Variant protein T94936_PEA_1_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA_1_P3 5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positidn(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 104 T ->A No 28 K->R No Variant protein T94936_PEA-lP3 is encoded by the following transcript(s): 10 T94936_PEA-_T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T94936-PEAl-T2 is shown in bold; this coding portion starts at position 76 and ends at position 510. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein T94936_PEA__P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 158 A-> G No 186 A ->G No 385 A ->G No 746 T-> C No 889 A -> C No 889 A -> G No WO 2005/072050 PCT/IB2005/000433 437 980 A-> No 1006 A -> No 1105 A-> No 1356 A ->G No As noted above, cluster T94936 features 12 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster T94936_PEA_1_node_14 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA_1_T2. Table 8 below describes the 10 starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA-_T2 443 803 Segment cluster T94936_PEA_1-node_16 according to the present invention is supported 15 by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEAl-T2. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_T2 804 1213 20 Segment cluster T94936_PEAInode_2 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 438 can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEA_1_T2. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 49 184 T94936_PEA_1_T2 49 184 5 Segment cluster T94936_PEA _1node_20 according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEAl-T2. Table 11 below describes the starting and ending position of this segment on each transcript. 10 Table ]] - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936-PEA-lT2 1298 1526 Segment cluster T94936_PEAInode_23 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): T94936_PEA-1_TI. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEAI _TI 527 751 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are 20 included in a separate description.

WO 2005/072050 PCT/IB2005/000433 439 Segment cluster T94936_PEA_1_node_0 according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEAITi and T94936_PEA_1_T2. Table 13 below describes the starting and ending position of this segment on each transcript. 5 Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 1 48 T94936_PEA_1_T2 1 48 Segment cluster T94936_PEA_1_node_11 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEA_1_T2. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 302 378 T94936-PEAIT2 302 378 15 Segment cluster T94936_PEA_1_node_13 according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEA_1_T2. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 379 442 T94936_PEA-lT2 379 442 20 WO 2005/072050 PCT/IB2005/000433 440 Segment cluster T94936_PEA_1_node_17 according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA_1_Ti and T94936_PEA-lT2. Table 5 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position. T94936_PEA_1_Ti 443 526 T94936_PEA_1_T2 1214 1297 Segment cluster T94936_PEA_1_node_6 according to the present invention is supported 10 by 74 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEAIT2. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_Ti 185 248 T94936_PEAIT2 185 248 15 Segment cluster T94936_PEA-_1node_8 according to the present invention can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEA_1-T2. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 249 252 T94936_PEA _T2 249 252 20 WO 2005/072050 PCT/IB2005/000433 441 Segment cluster T94936_PEA_1_node_9 according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA_1_TI and T94936_PEA_1_T2. Table 5 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position T94936_PEA_1_TI 253 301 T94936_PEA_1_T2 253 301 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/lR8BEXWutz/cdFRKHIcZR:Q8TDO6 Sequence documentation: 15 Alignment of: T94936_PEA_1_P2 x Q8TD06 Alignment segment 1/1: 20 Quality: 1486.00 Escore: 0 Matching length: 150 Total length: 150 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 442 Gaps: 0 Alignment: 5 1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50 1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50 51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100 10 51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100 101 MHETTDKNLSPDGQYVPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL 150 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l lI IIIll l l l l l l l l l lI I 15 101 MHETTDKNLSPDGQYVPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL 150 20 Sequence name: /tmp/AG3unOON3y/kjgGehygST:Q8TDO6 Sequence documentation: 25 Alignment of: T94936_PEA_1_P3 x Q8TDO6 Alignment segment 1/1: 30 Quality: 1214.00 Escore: 0 WO 2005/072050 PCT/IB2005/000433 443 Matching length: 122 Total length: 122 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 10 . 1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50 1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50 15 51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100 51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100 101 MHETTDKNLSPDGQYVPRIMFV 122 20 I l l l l l l l l1 l1 l l l l l l l l l 101 MHETTDKNLSPDGQYVPRIMFV 122 25 Expression of Homo sapiens breast cancer membrane protein 11 (BCMP1 1) T94936 transcripts which are detectable by amplicon as depicted in sequence name T94936 segl4 in normal and cancerous Breast tissues Expression of Homo sapiens breast cancer membrane protein 11 (BCMP 11) transcripts 30 detectable by or according to segl4, T94936 segl4 amplicon(s) and T94936 segl4F and T94936 segl4R primers was measured by real time PCR. In this specific example, the real-time PCR WO 2005/072050 PCT/IB2005/000433 444 reaction efficiency was assumed to be 2 and was not calculated by a standard curve reaction (as detailed above in the section of "Real-Time RT-PCR analysis"). In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), 5 SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 10 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up regulation for each sample relative to median of the normal PM samples. Figure 23 is a histogram showing over expression of the above-indicated Homo sapiens breast cancer membrane protein 11 (BCMP 11) transcripts in cancerous breast samples relative to the normal samples. 15 As is evident from Figure 23, the expression of Homo sapiens breast cancer membrane protein 11 (BCMP 11) transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"). Notably an over-expression of at least 5 fold was found in 17 out of 28 adenocarcinoma samples. 20 Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of Homo sapiens breast cancer membrane protein 11 (BCMP 11) transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 7.94E-02. 25 Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.74E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

WO 2005/072050 PCT/IB2005/000433 445 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: T94936 segl4F forward primer; and T94936 segl4R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: T94936 seg14. T94936 segl4 Forward primer (SEQ ID NO:859): TACAAAATTAGTAGAAATCAGCATTCTTGC 10 T94936 segl4 Reverse primer (SEQ ID NO:860): TGTAGAACTAACAAGAGCTGATATTATTGGAT T94936 segl4 Amplicon (SEQ ID NO:861): TACAAAATTAGTAGAAATCAGCATTCTTGCTTTTATTTTTAAATGCTAGTTCAAGTA CTATTCTTTTTAAAGAGAAGTCATTTCTAATCCAATAATATCAGCTCTTGTTAGTTCT 15 ACA DESCRIPTION FOR CLUSTER Z41644 Cluster Z41644 features 1 transcript(s) and 21 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 20 application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name' Sequence JU) No Z41644_PEA_1_T5 208 Table 2 - Segments of interest Segment Name Sequence 11) No. Z41644_PEA_1_node_0 209 Z41644_PEA_1_node_11 210 Z41644_PEA_1_node_12 211 WO 2005/072050 PCT/IB2005/000433 446 Z41644_PEA 1 node 15 212 Z41644_PEA_1_node 20 213 Z41644_PEA_1_node_24 214 Z41644_PEA-1 node 1 215 Z41644_PEA 1 node 10 216 Z41644_PEA_1 node 13 217 Z41644_PEA-I-node 16 218 Z41644_PEA_1 node 17 219 Z41644_PEA_1_node 19 220 Z41644_PEA_1_node-2 221 Z41644_PEA_1_node_21 222 Z41644_PEA_1_node_22 223 Z41644_PEA_1_node_23 224 Z41644_PEAInode_25 225 Z41644_PEA lnode 3 226 Z41644_PEA_-node_4 227 Z41644_PEAInode_6 228 Z41644_PEA_1_node_9 229 Table 3 - Proteins of interest Protein Name Sequence 1) No. Z41644_PEA_1_P1O 231 These sequences are variants of the known protein Small inducible cytokine B14 5 precursor (SwissProt accession identifier SZ14_HUMAN; known also according to the synonyms CXCL14; Chemokine BRAK), SEQ ID NO: 230, referred to herein as the previously known protein. Protein Small inducible cytokine B 14 precursor is known or believed to have the following function(s): Not chemotactive for T-cells, B-cells, monocytes, natural killer cells or 10 ghranulocytes. Does not inhibit proliferation of myeloid progenitors in colony formation assays.

WO 2005/072050 PCT/IB2005/000433 447 The sequence for protein Small inducible cytokine B14 precursor is given at the end of the application, as "Small inducible cytokine B14 precursor amino acid sequence". Protein Small inducible cytokine B14 precursor localization is believed to be Secreted. The following GO Annotation(s) apply to the previously known protein. The following 5 annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available 10 from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster Z41644 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of 15 the table and the numbers on the y-axis of Figure 24 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 20 Figure 24 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: lung malignant tumors, breast malignant tumors and pancreas carcinoma. Table 4 - Normal tissue distribution Name of Tissue Number bone 45 brain 62 colon 327 epithelial 179 general 104 head and neck 10 WO 2005/072050 PCT/IB2005/000433 448 kidney 219 lung 6 lymph nodes 37 breast 87 bone marrow 0 muscle 20 ovary 36 Pancreas 0 prostate 78 skin 591 stomach 109 Thyroid 386 uterus 218 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 bone 4.9e-01 8.5e-01 1.8e-01 1.9 5.3e-01 1.0 brain 6.7e-01 8.Oe-01 9.le-01 0.6 9.9e-01 0.4 colon 6.4e-01 7.7e-01 9.7e-01 0.4 1 0.3 epithelial 4.le-01 9.4e-Ol 9.6e-01 0.7 1 0.4 general 1.5e-01 9.4e-01 1.8e-01 1.0 1 0.5 head and neck 1.9e-01 3.3e-01 4.6e-01 2.8 7.5e-01 1.5 kidney 7.7e-01 8.2e-01 7.0e-01 0.7 9.5e-01 0.5 lung 2.2e-01 5.0e-01 1.3e-04 8.7 8.le-03 4.1 lymph nodes 6.3e-01 8.7e-01 6.3e-01 1.2 9.2e-01 0.6 breast 4.0e-01 6.5e-01 3.9e-04 3.5 2.9e-02 1.9 bone marrow 1 6.7e-01 1 1.0 5.3e-01 1.9 muscle 5.2e-01 6.le-01 2.7e-01 3.2 6.3e-01 1.2 ovary 6.7e-01 7.le-01 7.6e-01 1.0 8.6e-01 0.8 WO 2005/072050 PCT/IB2005/000433 449 pancreas 2.2e-02 2.3e-02 5.7e-03 7.8 1.6e-03 8.2 prostate 8.8e-01 9.0e-01 8.3e-01 0.6 9.3e-01 0.5 skin 5.9e-01 6.9e-01 2.3e-01 0.3 1 0.0 stomach 6.le-01 8.9e-01 8.le-01 0.7 9.9e-01 0.4 Thyroid 7.0e-01 7.0e-01 9.9e-01 0.4 9.9e-01 0.4 uterus 5.3e-01 8.2e-01 9.5e-01 0.5 1 0.3 As noted above, cluster Z41644 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible cytokine B 14 precursor. A description of each variant protein according to the present invention is now provided. 5 Variant protein Z41644_PEA_1_PlO according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z41644_PEA_1_T5. An alignment is given to the known protein (Small inducible cytokine B14 precursor) at the end of the application. One or more alignments to one or more previously 10 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z41644_PEA_1-P1O and SZ14_HUMAN: 1.An isolated chimeric polypeptide encoding for Z41644_PEA-1_PlO, comprising a first 15 amino acid sequence being at least 90 % homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1 95 of SZ14_HJIUMAN, which also corresponds to amino acids 1 - 95 of Z41644_PEA_1_P1O, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 20 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to amino acids 96 - 123 of Z41644_PEA-1_P10, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z41644-PEA._1-P10, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 450 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA_1_P1O. Comparison report between Z41644_PEA_1_PlO and Q9NS21 (SEQ ID NO:862): 1.An isolated chimeric polypeptide encoding for Z41644_PEA_1_P10, comprising a first 5 amino acid sequence being at least 90 % homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13 107 of Q9NS21, which also corresponds to amino acids 1 - 95 of Z41644_PEA_1_P1O, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 10 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to amino acids 96 - 123 of Z41644_PEA_1_P1O, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z41644_PEA-1_P10, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA_1_PlO. Comparison report between Z41644_PEA_1_PlO and AAQ89265 (SEQ ID NO:863): 1.An isolated chimeric polypeptide encoding for Z41644_PEA-1-P10, comprising a first 20 amino acid sequence being at least 90 % homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13 107 of AAQ89265, which also corresponds to amino acids 1 - 95 of Z41644_PEA_1_P10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 25 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI corresponding to amino acids 96 - 123 of Z41644-PEA_1._P1, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z41644_PEA-1_P10, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 451 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI in Z41644_PEA_1_PO. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein Z41644_PEA_1_PIO also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indic ates whether the SNP is known or not; the presence of known SNPs in variant protein Z41644_PEA_1_PlO sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 6 - Amino acid mutations NP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 32 P -> H Yes 64 S-> No 80 T-> A No 80 T-> P No Variant protein Z41644_PEA-1_PIO is encoded by the following transcript(s): Z41644_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The 20 coding portion of transcript Z41644_PEA_1_T5 is shown in bold; this coding portion starts at position 744 and ends at position 1112. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of WO 2005/072050 PCT/IB2005/000433 452 known SNPs in variant protein Z41644_PEA-1_P10 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 102 A ->G Yes 572 C-> No 3707 C -> T Yes 3735 C ->T Yes 4079 G ->A No 4123 G ->A Yes 4233 A ->G Yes 4328 C-> No 4350 A -> G Yes 4376 G ->A Yes 4390 A ->G Yes 4619 G ->T Yes 838 C -> A Yes 4754 C->T No 4757 C ->A No 4794 T-> G No 4827 G-> No 934 C -> No 981 A ->C No 981 A ->G No 1817 A ->C Yes 2546 T-> No 2684 T->A No 2885 T->C Yes WO 2005/072050 PCT/IB2005/000433 453 As noted above, cluster Z41644 features 21 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster Z41644-PEA_1_node_0 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 8 below describes the 10 starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 1 616 Segment cluster Z41644-PEA_1 node_I according to the present invention is supported 15 by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA-lT5. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 1028 2089 20 Segment cluster Z41644_PEAInode_12 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA-l_T5. Table 10 below describes the starting and ending position of this segment on each transcript. 25 Table 10 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 454 Transcript name Segment starting position Segment ending position Z41644_PEAIT5 2090 2350 Segment cluster Z41644_PEA_1 node_15 according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z41644_PEA_1_T5. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA 1_T5 2368 3728 10 Segment cluster Z41644_PEA_1_node_20 according to the present invention is supported by 260 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644-PEA-1_T5 3938 4506 15 Segment cluster Z41644_PEA_1_node_24 according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 13 below describes the 20 starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072050 PCT/IB2005/000433 455 Z41644_PEAIT5 4637 4799 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster Z41644_PEA_1_node_1 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644-PEA_1_T5. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEAIT5 617 697 10 Segment cluster Z41644_PEA_1_node_10 according to the present invention is supported by 138 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 15 below describes the 15 starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript nam e Segment starting position Segment ending position Z41644_PEA-lT5 972 1027 Segment cluster Z41644_PEA_1_node-13 according to the present invention can be 20 found in the following transcript(s): Z41644_PEA__T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 2351 2367 WO 2005/072050 PCT/IB2005/000433 456 Segment cluster Z41644_PEA-_1node_16 according to the present invention is supported by 152 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z41644_PEA_1_T5. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1 T5 3729 3809 10 Segment cluster Z41644_PEA-1_node_17 according to the present invention can be found in the following transcript(s): Z41644_PEA_1_T5. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA-1_T5 3810 3829 15 Segment cluster Z41644_PEA 1 node_19 according to the present invention is supported by 112 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 19 below describes the starting and ending position of this segment on each transcript. 20 Table 19 - Segment location on transcripts Transcript name' Segment starting position Segment ending position Z41644_PEA_1_T5 3830 3937 WO 2005/072050 PCT/IB2005/000433 457 Segment cluster Z41644_PEA_1_node_2 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 20 below describes the starting and ending position of this segment on each transcript. 5 Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 698 737 Segment cluster Z41644_PEA_1_node_21 according to the present invention can be found in the following transcript(s): Z41644_PEA_1_T5. Table 21 below describes the starting 10 and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 4507 4529 Segment cluster Z41644_PEA_1_node_22 according to the present invention is supported 15 by 164 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1-T5. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644-PEA_1_T5 4530 4582 20 Segment cluster Z41644_PEA_1_node_23 according to the present invention is supported by 169 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 458 can be found in the following transcript(s): Z41644_PEA_1_T5. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 4583 4636 5 Segment cluster Z41644_PEA_1-node_25 according to the present invention is supported by 138 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644-PEA_1_T5. Table 24 below describes the starting and ending position of this segment on each transcript. 10 Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 4800 4902 Segment cluster Z41644_PEA_1_node_3 according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Z41644-PEA_1_T5. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA 1_T5 738 773 20 Segment cluster Z41644_PEA_1_node_4 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 26 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 459 Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending positiq Z41644_PEA_1_T5 774 807 Segment cluster Z41644_PEA_1_node_6 according to the present invention is supported 5 by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 808 913 10 Segment cluster Z41644_PEA_-node_9 according to the present invention is supported by 134 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA_1_T5. Table 28 below describes the starting and ending position of this segment on each transcript. 15 Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z41644_PEA_1_T5 914 971 Variant protein alignment to the previously known protein: 20 Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:SZ14_HUMAN Sequence documentation: WO 2005/072050 PCT/IB2005/000433 460 Alignment of: Z41644_PEA_1_PlO x SZ14_HUMAN . . Alignment segment 1/1: 5 Quality: 953.00 Escore: 0 Matching length: 95 Total length: 95 Matching Percent Similarity: 100.00 Matching Percent 10 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50 11 11| 1i~ I I I |liii I 1 ||||1 |III||||IlII11 111 1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50 20 . 51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95 lI I I I I |1 1 I 1 1| | | || I l I | I I I I I I1 1 | I | | | || | | |1 51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95 25 30 Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:Q9NS21 WO 2005/072050 PCT/IB2005/000433 461 Sequence documentation: Alignment of: Z41644_PEA_1_PlO x Q9NS21 5 Alignment segment 1/1: Quality: 957.00 Escore: 0 Matching length: 96 Total 10 length: 96 Matching Percent Similarity: 100.00 Matching Percent Identity: 98.96 Total Percent Similarity: 100.00 Total Percent Identity: 98.96 15 Gaps: 0 Alignment: 1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50 2 01I 1 1l l i l l l i l l i l l l l l I l l l l l l l l l l l l l l l l l l l l l l l l l1 13 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 62 51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRY 96 25 63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRF 108 30 WO 2005/072050 PCT/IB2005/000433 462 Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:AAQ89265 Sequence documentation: 5 Alignment of: Z41644_PEA_1_PlO x AAQ89265 Alignment segment 1/1: Quality: 953.00 10 Escore: 0 Matching length: 95 Total length: 95 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50 13 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 62 25 51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95 63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 107 30 DESCRIPTION FOR CLUSTER M85491 WO 2005/072050 PCT/IB2005/000433 463 Cluster M85491 features 2 transcript(s) and 11 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table ] - Transcripts of interest Transcript Name Sequence ID No. M85491_PEA_1 T16 232 M85491_PEA_1 T20 233 5 Table 2 - Segments of interest Segment Name Sequence ID No. M85491-PEA-_1node_0 234 M85491_PEAI node_13 235 M85491_PEA-_1node_21 236 M85491_PEA-1-node_23 237 M85491_PEA_-node_24 238 M85491_PEA_1_node_8 239 M85491_PEA_1-node_9 240 M85491-PEA_1_node_10 241 M85491_PEA_1-node_18 242 M85491_PEA_1_node_19 243 M85491_PEA_1_node_6 244 Table 3 - Proteins of interest Protein Name Sequence ID No. M85491_PEA_1_P13 246 M85491-PEA-1_P14 .247 10 These sequences are variants of the known protein Ephrin type-B receptor 2 [precursor] (SwissProt accession identifier EPB2-HUMAN; known also according to the synonyms EC WO 2005/072050 PCT/IB2005/000433 464 2.7.1.112; Tyrosine-protein kinase receptor EPH-3; DRT; Receptor protein-tyrosine kinase HEKS; ERK), SEQ ID NO: 245, referred to herein as the previously known protein. Protein Ephrin type-B receptor 2 [precursor] is known to have the following function(s): Receptor for members of the ephrin-B family. The sequence for protein Ephrin type-B receptor 5 2 [precursor] is given at the end of the application, as "Ephrin type-B receptor 2 [precursor] amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNPposition(s) on Comment amino acid sequence 671 A ->R. /FTId=VAR004162. 1 20 MALRRLGAALLLLPLLAAVE -> MWVPVLALPVCTYA 923 E ->K 956 L ->V 958 V->L 154 G -> D 476 K->KQ 495 - 496 Missing 532 E->D 568 R->RR 589 M -> I 788 I -> F 853 S -> A Protein Ephrin type-B receptor 2 [precursor] localization is believed to be Type I 10 membrane protein. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein amino acid phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; neurogenesis, which are annotation(s) related to Biological WO 2005/072050 PCT/IB2005/000433 465 Process; protein tyrosine kinase; receptor; transmembrane-ephrin receptor; ATP binding; transferase, which are annotation(s) related to Molecular Function; and integral membrane protein, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl 5 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster M85491 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 10 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 25 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 15 Overall, the following results were obtained as shown with regard to the histograms in Figure 25 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues. 20 Table 5 - Normal tissue distribution Name of Tissue Number Bladder 0 Bone 0 Brain 10 Colon 31 epithelial 10 general 12 Kidney 0 Liver 0 Lung 5 WO 2005/072050 PCT/IB2005/000433 4 66 Breast 8 Muscle 5 Ovary 36 pancreas 10 Skin 0 stomach 0 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1' P2 SPI R3 SP2 R4 bladder 5.4e-01 6.0e-01 3.2e-01 2.5 4.6e-01 1.9 Bone 1 2.8e-01 1 1.0 7.0e-01 1.8 Brain 3.4e-01 3.6e-01 1.2e-O1 2.9 1.8e-02 2.7 Colon 3.4e-02 5.7e-02 8.2e-02 2.8 2.0e-01 2.1 epithelial 1.7e-03 3.5e-03 2.0e-03 2.8 1.le-02 2.2 general 4.8e-04 5.2e-04 6.7e-04 2.3 1.3e-03 1.9 Kidney 4.3e-01 3.7e-01 1 1.1 7.0e-01 1.5 Liver I 4.5e-01 1 1.0 6.9e-01 1.5 Lung 2.2e-01 2.7e-01 6.9e-02 3.6 3.4e-02 3.6 Breast 8.2e-01 7.3e-01 6.9e-01 1.2 6.8e-01 1.2 Muscle 9.2e-01 4.8e-01 1 0.8 1.5e-01 3.2 Ovary 8.5e-01 7.3e-01 9.0e-01 0.7 6.7e-01 1.0 pancreas 5.5e-01 2.0e-01 6.7e-01 1.2 3.5e-01 1.8 Skin 2.9e-01 4.7e-01 1.4e-01 7.0 6.4e-01 1.6 stomach 1.5e-01 3.2e-01 1 1.0 8.0e-01 1.3 As noted above, cluster M85491 features 2 transcript(s), which were listed in Table 1 5 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ephrin type-B receptor 2 [precursor]. A description of each variant protein according to the present invention is now provided.

WO 2005/072050 PCT/IB2005/000433 467 Variant protein M85491_PEA_1_P13 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M85491_PEA_1_T16. An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously 5 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between M85491-PEA_1-P13 and EPB2_HUMAN: 10 1.An isolated chimeric polypeptide encoding for M85491-PEA_1_P13, comprising a first amino acid sequence being at least 90 % homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVF ESSQNNWLRTKFIRRRGAHRIHIVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF 15 YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN SRTTSEGATNCVCRNGYYRADLDPLDMCTTIPSAPQAVISSVNETSLMLEWTPPRDSG GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL 20 QYYEK corresponding to amino acids 1 - 476 of EPB2-HIUMAN, which also corresponds to amino acids 1 - 476 ofM85491-PEA_1-P13, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG corresponding to amino acids 477 - 496 of 25 M85491-PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of M85491-PEA__P 13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 30 sequence VPIGWVLSPSPTSLRAPLPG in M85491_PEA_1_P13.

WO 2005/072050 PCT/IB2005/000433 468 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein M85491-PEA-__P13 is encoded by the following transcript(s): M85491_PEA_1_T16, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA_1_T16 is shown in bold; this coding portion starts at position 143 and 10 ends at position 1630. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA_1_P13 sequence provides support for the deduced sequence of this variant protein according to the present invention). 15 Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 799 G ->A Yes 1066 C ->T Yes 1519 A ->G Yes 1872 C->T Yes 2044 T-> C Yes 2156 G->A Yes 2606 C -> A Yes 2637 G -> C Yes Variant protein M85491-PEA-l_P14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 20 M85491_PEA-lT20. An alignment is given to the known protein (Ephrin type-B receptor 2 WO 2005/072050 PCT/IB2005/000433 469 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between M85491_PEA_1_P14 and EPB2_HUMAN: 1.An isolated chimeric polypeptide encoding for M85491_PEA_1-P14, comprising a first amino acid sequence being at least 90 % homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR 10 TYQVCNVFESSQNNWLRTKFIRRRGAHRIHIVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1 270 of EPB2_HUMAN, which also corresponds to amino acids 1 - 270 of 15 M85491_PEA_1 P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL corresponding to amino acids 271 - 301 of M85491_PEA_1-P14, wherein said first and second amino acid sequences are contiguous and 20 in a sequential order. 2.An isolated polypeptide encoding for a tail of M85491-PEA_1_P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL in M85491_PEA_1_P14. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows withregard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 30 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

WO 2005/072050 PCT/IB2005/000433 470 Variant protein M85491_PEA_1_P14 is encoded by the following transcript(s): M85491_PEA_1_T20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA_1_T20 is shown in bold; this coding portion starts at position 143 and ends at position 1045. The transcript also has the following SNPs as listed in 5 Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA_1_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 799 G ->A, Yes 1135 T-> C Yes 1160 T-> C Yes 1172 A-> C Yes 1176 T-> A Yes 10 As noted above, cluster M85491 features 11 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 15 Segment cluster M85491_PEA_1_node_0 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16 and M85491-PEA_1_T20. Table 9 below describes the starting and ending position of this segment on each transcript. 20 Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEAI_T16 1 203 WO 2005/072050 PCT/IB2005/000433 471 M85491_PEAlT20 203 Segment cluster M85491_PEA_1_node_13 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): M85491_PEA_1_T20. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEAIT20 954 1182 Segment cluster M85491_PEA_1_node_21 according to the present invention is 10 supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 1110 1445 15 Segment cluster M85491-PEA_1_node-23 according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16. Table 13 below describes the starting and ending position of this segment on each transcript. 20 Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEAI_T16 1446 1570 WO 2005/072050 PCT/IB2005/000433 472 Segment cluster M85491_PEA_1_node_24 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16. Table 14 below describes the starting and ending position of this segment on each transcript. 5 Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 1571 2875 Segment cluster M85491_PEA_1_node_8 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): M85491_PEAI_T16 and M85491-PEA-lT20. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA-_T16 269 672 M85491_PEA_1_T20 269 672 Segment cluster M85491_PEA_1_node_9 according to the present invention is supported 15 by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16 and M85491_PEA-_T20. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 673 856 M85491_PEA_1_T20 673 856 According to an optional embodiment of the present invention, short segments related to 20 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

WO 2005/072050 PCT/IB2005/000433 473 Segment cluster M85491-PEA_1_node_10 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16 and 5 M85491_PEA_1_T20. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 857 953 M85491_PEA_1_T20 857 953 10 Segment cluster M85491_PEA_1_node_18 according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491-PEA_1_T16. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 954 1044 15 Segment cluster M85491_PEA_1_node_19 according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16. Table 20 below 20 describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEAIT16 1045 1109 WO 2005/072050 PCT/IB2005/000433 474 Segment cluster M85491_PEAI_ ode_6 according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16 and M85491_PEA_1_T20. 5 Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1 T16 204 268 M85491_PEA_1_T20 204 268 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/qfmsU9VtxS/DylcLC9j8v:EPB2_HUMAN Sequence documentation: 15 Alignment of: M85491_PEA_1_P13 x EPB2_HUMAN Alignment segment 1/1: 20 Quality: 4726.00 Escore: 0 Matching length: 476 Total length: 476 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 475 Gaps: 0 Alignment: 5 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 10 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 15 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 i l l l 111l11I|||||||1|| | | | | | l II l 1l i 11l|||| I lI l 11l 11111II 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 20 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 I l i I 1|| 1| I 1 1|| | 1| | || 1 I 1 | | | |1 I| | | 1 |1 | | | | | ||1 I II 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 25 251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300 251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300 301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350 310 | | | |I I I | |1| | I|1 1 l l | | | | | | | III| | | | || | || | | | | 1 | | 0 301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350 WO 2005/072050 PCT/IB2005/000433 476 351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400 351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400 5 401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450 || | | I |I I II 111|1 || I 1I 11 I||1l II1111 I||| || 1||||| 401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450 10 451 SITLSWSQPDQPNGVILDYELQYYEK 476 451 SITLSWSQPDQPNGVILDYELQYYEK 476 15 Sequence name: /tmp/rmnzuDbot6/GiHbjeU8iR:EPB2_HUMAN 20 Sequence documentation: Alignment of: M85491_PEA_1_P14 x EPB2_HUMAN 25 Alignment segment 1/1: Quality: 2673.00 Escore: 0 Matching length: 270 Total 30 length: 270 WO 2005/072050 PCT/IB2005/000433 477 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 10 | 1 1 1 1 1 |11 111 1 1 I~l l I l1l1l1||| l | 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 I1 1 1 1 I 1||11| |||1111|| 1|| | 1 | | |1 |11 | 11 | 15 .51 ENMNTIRTYQVCNVFESSQNNWLRTKFIlRRRGAHRIHVEMKFSVRDCSSI 100 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 20 . . . 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 | |1 ||111 1 1| 1| 1|1 |11 i i 1 1 1 1 I I | |1||1|||1||| || |1 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 25 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 251 IGRCMCKAGFEAVENGTVCR 270 30 ||| |1 ||| | 1 11 |11 ||| 251 IGRCMCKAGFEAVENGTVCR 270 WO 2005/072050 PCT/IB2005/000433 478 Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase 5 receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in normal and cancerous breast tissues Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by or according to seg24, M85491seg24 amplicon and M85491seg24F M85491seg24R primers was measured by real time PCR. In parallel the 10 expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1 amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of 15 the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up regulation for each sample relative to median of the normal PM samples. Figure 26 is a histogram showing over expression of the above- indicated Ephrin type-B 20 receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts in cancerous breast samples relative to the normal samples. As is evident from Figure 26, the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon in a few cancer samples was higher than in the non-cancerous samples (Sample Nos. 25 56-60, 63-67, Table 1, above, "Tissue samples in testing panel").

WO 2005/072050 PCT/IB2005/000433 479 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: M8549 1 seg24F forward primer; and M85491seg24R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: M85491seg24. M85491seg24 Forward primer (SEQ ID NO:864): GGCGTCTTTCTCCCTCTGAAC M85491seg24 Reverse primer (SEQ lID NO:865): GTCCCATTCTGGGTGCTGTG 10 M85491seg24 Amplicon (SEQ ID NO:866): GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGTGAGACCC CTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGCACCCAGAATGGG AC 15 Expression of Ephrin type-B receptor 2 precursorM85491 transcripts, which are detectable by amplicon as depicted in sequence name M85491 seg24 in different normal tissues 20 Expression of Ephrin type-B receptor 2 precursor transcripts detectable by or according to M85491 seg24 amplicon(s) and M85491 seg24F and M85491 seg24R priemrs was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon 25 Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA amplicon) was measured similarly. For each RT sample, the expression of the above armplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the colon samples (Sample Nos. 1-3 Table 2,"Tissue samples on normal pawl", above), to obtain a 30 value of relative expression of each sample relative to median of the colon samples. Primers and amplicon are as above.

WO 2005/072050 PCT/IB2005/000433 480 The results are presented in Figure 27, demonstrating the expression of Ephrin type-B receptor 2 precursor M85491 transcripts, which are detectable by amplicon as depicted in sequence name M85491 seg24, in different normal tissues. 5 DESCRIPTION FOR CLUSTER HSSTROL3 Cluster HSSTROL3 features 6 transcript(s) and 16 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 10 Table 1 - Transcripts of interest Transcript Name Sequence ID No. HSSTROL3_T5 248 HSSTROL3_T8 249 HSSTROL3-T9 250 HSSTROL3TI10 251 HSSTROL3_T1 1 252 HSSTROL3_T12 253 Table 2 - Segments of interest Segment Name Sequence ID No. HSSTROL3_node_6 254 HSSTROL3_node 10 255 HSSTROL3_node_13 256 HSSTROL3_node 15 257 HSSTROL3_node_19 258 HSSTROL3_node 21 259 HSSTROL3_node_24 260 HSSTROL3-node_25 261 HSSTROL3_node_26 262 WO 2005/072050 PCT/IB2005/000433 481 HSSTROL3_node_28 263 HSSTROL3_node 29 264 HSSTROL3_node 11 265 HSSTROL3_node_17 266 HSSTROL3_node 18 267 HSSTROL3_node 20 268 HSSTROL3_node_27 269 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) HSSTROL3_P4 271 HSSTROL3_T5 HSSTROL3_P5 272 HSSTROL3_T8; HSSTROL3_T9 HSSTROL3_P7 273 HSSTROL3_T1O HSSTROL3_P8 274 HSSTROL3_T II HSSTROL3_P9 275 HSSTROL3-T12 These sequences are variants of the known protein Stromelysin-3 precursor (SwissProt 5 accession identifier MM1 1_HIIUMAN; known also according to the synonyms EC 3.4.24.-; Matrix metalloproteinase-11; MMP- 11; ST3; SL-3), SEQ ID NO: 270, referred to herein as the previously known protein. Protein Stromelysin-3 precursor is known or believed to have the following function(s): May play an important role in the progression of epithelial malignancies. The sequence for 10 protein Stromelysin-3 precursor is given at the end of the application, as "Stromelysin-3 precursor amino acid sequence". The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: proteolysis and peptidolysis; developmental processes; morphogenesis, which are annotation(s) related to Biological Process; stromelysin 3; calcium 15 binding; zinc binding; hydrolase, which are annotation(s) related to Molecular Function; and extracellular matrix, which are annotation(s) related to Cellular Component.

WO 2005/072050 PCT/IB2005/000433 482 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 5 Cluster HSSTROL3 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 28 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to 10 the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 28 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: transitional cell carcinoma, epithelial malignant tumors, a 15 mixture of malignant tumors from different tissues and pancreas carcinoma. Table 4 - Normal tissue distribution Name of Tissue Number Adrenal 0 Bladder 0 Brain 1 Colon 63 Epithelial 33 General 13 head and neck 101 Kidney 0 lung I1 breast 8 WO 2005/072050 PCT/IB2005/000433 483 ovary 14 pancreas 0 prostate 2 skin 99 Thyroid 0 uterus 181 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 R3 SP2 R4 adrenal 1 4.6e-01 1 1.0 5.3e-01 1.9 bladder 2.7e-01 3.4e-01 3.3e-03 4.9 2.le-02 3.3 brain 3.5e-01 2.6e-01 1 1.7 3.3e-01 2.8 colon 7.7e-02 1.5e-01 3.le-O1 1.4 5.2e-01 1.0 epithelial 1.2e-04 1.2e-02 1.3e-06 2.7 4.6e-02 1.4 general 5.4e-09 3.le-05 1.Se-16 5.0 3.le-07 2.6 head and neck 4.6e-01 4.3e-01 1 0.6 9.4e-01 0.7 kidney 2.5e-01 3.5e-01 1.le-01 4.0 2.4e-01 2.8 lung 1.8e-01 4.5e-01 1.9e-01 2.7 5.le-01 1.4 breast 2.0e-01 3.4e-01 7.3e-02 3.3 2.5e-01 2.0 ovary 2.6e-01 3.2e-01 2.2e-02 2.0 7.0e-02 1.6 pancreas 9.5e-02 1.8e-01 1.8e-04 7.8 1.6e-03 5.5 prostate S.2e-01 7.8e-01 4.5e-01 1.8 5.6e-01 1.5 skin 5.2e-01 5.8e-01 7.le-01 0.8 1 0.3 Thyroid 2.9e-01 2.9e-01 1 1.1 1 1.1 uterus 4.2e-01 8.Oe-01 7.5e-01 0.6 9.9e-01 0.4 As noted above, cluster HSSTROL3 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Stromelysin-3 5 precursor. A description of each variant protein according to the present invention is now provided.

WO 2005/072050 PCT/IB2005/000433 484 Variant protein HSSTROL3_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T5. An alignment is given to the known protein (Stromelysin-3 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are 5 given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSSTROL3_P4 and MMI 1_HUMAN: 1.An isolated chimeric polypeptide encoding for HSSTROL3_P4, comprising a first amino acid sequence being at least 90 % homologous to 10 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1 - 163 of MM1 1_HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3_P4, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4, 15 a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPE 20 KNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG corresponding to amino acids 165 - 445 of MMI 1-HUMAN, which also corresponds to amino acids 165 - 445 of HSSTROL3_P4, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG corresponding to amino acids 446 - 496 of HSSTROL3_P4, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSSTROL3_P4, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the WO 2005/072050 PCT/IB2005/000433 485 sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG in HSSTROL3_P4. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HSSTROL3_P4 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P4 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 6 -Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 38 V-> A Yes 104 R->P Yes 214 A -> No 323 Q -> H Yes Variant protein HSSTROL3_P4 is encoded by the following transcript(s): HSSTROL3_T5, for which the sequence(s) is/are given at the end of the application. The coding 20 portion of transcript HSSTROL3_T5 is shown in bold; this coding portion starts at position 24 and ends at position 1511. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in WO 2005/072050 PCT/IB2005/000433 486 variant protein HSSTROL3-P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T->C Yes 334 G -> C Yes 663 G-> No 699 -> T No 992 G -> C Yes 1528 A -> G Yes 1710 A -> G Yes 2251 A ->G Yes 2392 C-> No 2444 C ->A Yes 2470 A ->T Yes 2687 -> G No 2696 -> G No 2710 C -> No 2729 -> A No 2755 T-> C No 2813 A-> No 2813 A ->C No 2963 A-> No 2963 A ->C No 2993 T -> C Yes 3140 ->T No 5 WO 2005/072050 PCT/IB2005/000433 487 Variant protein HSSTROL3_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T8 and HSSTROL3-T9. An alignment is given to the known protein (Stromelysin-3 precursor) at the end of the application. One or more alignments to one or more previously published protein 5 sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSSTROL3-P5 and MM1 1_HUMAN: 1 .An isolated chimeric polypeptide encoding for HSSTROL3_P5, comprising a first amino acid sequence being at least 90 % homologous to 10 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVltQTMAEALKVWSDVTPLTFTEVHEGRADlIlDFARYW corresponding to amino acids 1 - 163 of MMi 1_HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3-P5, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5, 15 a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165 - 358 of MMl 1_HUMAN, 20 which also corresponds to amino acids 165 - 358 of HSSTROL3_P5, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK corresponding to amino acids 359 - 382 of HSSTROL3_P5, wherein said first amino acid sequence, bridging amino acid, second amino 25 acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSSTROL3_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK in HSSTROL3_P5. 30 WO 2005/072050 PCT/IB2005/000433 488 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSSTROL3_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP positions) on amino acid Alternative amino acids) Previously known SNP? sequence 38 V->A Yes 104 R->P Yes 214 A -> No 323 Q -> H Yes 15 Variant protein HSSTROL3_P5 is encoded by the following transcript(s): HSSTROL3_T8 and HSSTROL3_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T8 is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as 20 listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucle ic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 489 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T->C Yes 334 G -> C Yes 663 G-> No 699 -> T No 992 G -> C Yes 1903 C -> No 1955 C -> A Yes 1981 A->T Yes 2198 ->G No 2207 ->G No 2221 C-> No 2240 -> A No 2266 T->C No 2324 A-> No 2324 A -> C No 2474 A -> No 2474 A -> C No 2504 T->C Yes 2651 -> T No The coding portion of transcript HSSTROL3_T9 is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the 5 alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 490 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T->C Yes 334 G-> C Yes 663 G-> No 699 -> T No 992 G -> C Yes 1666 A ->G Yes 1848 A ->G Yes 2389 A->G Yes 2530 C -> No 2582 C->A Yes 2608 A->T Yes 2825 ->G No 2834 ->G No 2848 C-> No 2867 -> A No 2893 T->C No 2951 A-> No 2951 A->C No 3101 A-> No 3101 A -> C No 3131 T->C Yes 3278 -> T No Variant protein HSSTROL3_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T10. An alignment is given to the known protein (Stromelysin-3 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are 5 given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 491 Comparison report between HSSTROL3_P7 and MM1 1_HUMAN: 1.An isolated chimeric polypeptide encoding for HSSTROL3_P7, comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS 5 PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1 - 163 ofMM1 1_HUMAN, which also corresponds to amino acids 1 - 163 of HSSTROL3_P7, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7, a second amino acid sequence being at least 90 % homologous to 10 GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165 - 359 of MM1 1_HUMAN, which also corresponds to amino acids 165 - 359 of HSSTROL3_P7, and a third amino acid 15 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV corresponding to amino acids 360 - 370 of HSSTROL3_P7, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of HSSTROL3_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P7. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 30 region prediction program predicts that this protein has a trans-membrane region.

WO 2005/072050 PCT/IB2005/000433 492 Variant protein HSSTROL3_P7 also has the following non-silent SNPs (Single iIucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P7 5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 38 V->A Yes 104 R->P Yes 214 A -> No 323 Q -> H Yes Variant protein HSSTROL3_P7 is encoded by the following transcript(s): 10 HSSTROL3T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T1O is shown in bold; this coding portion starts at position 24 and ends at position 1133. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein HSSTROL3_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T-> C Yes 334 G -> C Yes 663 G -> No 699 -> T No WO 2005/072050 PCT/IB2005/000433 493 992 G-> C Yes 1386 A-> G Yes 1568 A-> G Yes 2109 A-> G Yes 2250 C -> No 2302 C -> A Yes 2328 A->T Yes 2545 -> G No 2554 -> G No 2568 C -> No 2587 -> A No 2613 T->C No 2671 A -> No 2671 A->C No 2821 A -> No 2821 A -> C No 2851 T->C Yes 2998 -> T No Variant protein HSSTROL3_P8 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T1 1. An alignment is given to the known protein (Stromelysin-3 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are 5 given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSSTROL3_P8 and MM1 1_HUMAN: 1.An isolated chimeric polypeptide encoding for HSSTROL3_P8, comprising a first amino acid sequence being at least 90 % homologous to 10 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1 - 163 of MM11_HUMAN, which also corresponds to amino acids 1 - 163 of WO 2005/072050 PCT/IB2005/000433 494 HSSTROL3_P8, a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P8, a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN 5 EIAPLE corresponding to amino acids 165 - 286 of MM 11_HUMAN, which also corresponds to amino acids 165 - 286 of HSSTROL3_P8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL corresponding to amino acids 287 - 301 of HSSTROL3_P8, wherein 10 said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSSTROL3_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence VRPCLPVPLLLCWPL in HSSTROL3_P8. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 20 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSSTROL3_P8 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the 25 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 495 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 38 V ->A Yes 104 R->P Yes 214 A -> No Variant protein HSSTROL3-PS is encoded by the following transcript(s): HSSTROL3_T 11, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T11 is shown in bold; this coding portion starts at 5 position 24 and ends at position 926. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T->C Yes 334 G -> C Yes 663 G -> No 699 -> T No 935 G -> A Yes 948 G -> A Yes 1084 G -> C Yes 1557 C-> No 1609 C -> A Yes 1635 A->T Yes 1852 -> G No 1861 -> G No WO 2005/072050 PCT/IB2005/000433 496 1875 C-> No 1894 -> A No 1920 T-> C No 1978 A-> No 1978 A->C No 2128 A -> No 2128 A->C No 2158 T->C Yes 2305 ->T No Variant protein HSSTROL3_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T12. 5 An alignment is given to the known protein (Stromelysin- 3 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSSTROL3_P9 and MIM IHUMAN: 10 1.An isolated chimeric polypeptide encoding for HSSTROL3-P9, comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1 96 of MM11_HUMAN, which also corresponds to amino acids 1 - 96 of HSSTROL3_P9, a 15 second amino acid sequence being at least 90 % homologous to R1LRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113 - 163 of MM1 1_HUMAN, which also corresponds to amino acids 97 - 147 of HSSTROL3_P9, a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9, a third amino acid sequence being at least 90 % homologous to 20 GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN

EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL

WO 2005/072050 PCT/IB2005/000433 497 PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165 - 359 of MM11 HUMAN, which also corresponds to amino acids 149 - 343 of HSSTROL3_P9, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 TTGVSTPAPGV corresponding to amino acids 344 - 354 of HSSTROL3_P9, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in 10 length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96; and ending at any of amino acid numbers 97+ ((n-2) - x), in which- x varies from 0 to n-2. 15 3.An isolated polypeptide encoding for a tail of HSSTROL3_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV in HSSTROL3_P9. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane 25 region prediction program predicts that this protein has a trans-membrane region. Variant protein HSSTROL3_P9 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 30 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072050 PCT/IB2005/000433 498 Table 15 - Amino acid mutations SNP. position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 38 V ->A Yes 198 A-> No 307 Q ->H Yes Variant protein HSSTROL3_P9 is encoded by the following transcript(s): HSSTROL3_T12, for which the sequence(s) is/are given at the end of the application. The 5 coding portion of transcript HSSTROL3_T12 is shown in bold; this coding portion starts at position 24 and ends at position 1085. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 sequence provides support for the deduced 10 sequence of this variant protein according to the present invention). Table 16 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 T ->C Yes 615 G-> No 651 -> T No 944 G -> C Yes 1275 C -> No 1327 C -> A Yes 1353 A->T Yes 1570 -> G No 1579 -> G No 1593 C -> No 1612 -> A No WO 2005/072050 PCT/IB2005/000433 499 1638 T->C No 1696 A -> No 1696 A-> C No 1846 A-> No 1846 A->C No 1876 T->C Yes 2023 -> T No As noted above, cluster HSSTROL3 features 16 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster HSSTROL3_node_6 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3-T8, HSSTROL3_T9, 10 HSSTROL3_T1O, HSSTROL3-Ti I and HSSTROL3_T12. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 1 131 HSSTROL3_T8 1 131 HSSTROL3_T9 1 131 HSSTROL3_TI0 1 131 HSSTROL3_TI1 1 131 HSSTROL3_T12 1 131 WO 2005/072050 PCT/IB2005/000433 500 Segment cluster HS STROL3_node_10 according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T 11 and HSSTROL3_T12. Table 18 below describes the 5 starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment Segment stating position ending position HSSTROL3_T5 132 313 HSSTROL3_T8 132 313 HSSTROL3_T9 132 313 HSSTROL3TIlO 132 313 HSSTROL3_T12 132 313 HSSTROL3_T12 132 313 Segment cluster HSSTROL3-node_13 according to the present invention is supported by 10 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_TS, HSSTROL3_T9, HSSTROL3-T1O, HSSTROL3_T11 and HSSTROL3_T12. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 362 505 HSSTROL3_T8 362 505 HSSTROL3_T9 362 505 HSSTROL3_T1O 362 505 HSSTROL3_TI 1 362 505 WO 2005/072050 PCT/IB2005/000433 501 HSSTROL3_T12 314 457 Segment cluster HSSTROL3_node_15 according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3-T10, HSSTROL3_T11 and HSSTROL3_T12. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3 T5 506 639 HSSTROL3 T8 506 639 HSSTROL3_T9 506 639 HSSTROL3_TIO 506 639 HSSTROL3_Ti 11 506 6 3 9 HSSTROL3_T12 458 591 10 Segment cluster HSSTROL3_node_19 according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_TI 1 and HSSTROL3_T12. Table 21 below describes the 15 starting and ending position of this segment on each transcript. Table 2] - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 699 881 HSSTROL3_T8 699 881 WO 2005/072050 PCT/IB2005/000433 502 HSSTROL3_T9 699 881 HSSTROL3_TIO 699 881 HSSTROL3_Tll 699 881 HSSTROL3_T12 651 833 Segment cluster HSSTROL3_node_21 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_TI0, HSSTROL3_T 1I and HSSTROL3_T12. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript, name Segment segment starting position ending position HSSTROL3 T5 882 1098 HSSTROL3_T8 882 1098 HSSTROL3_T9 882 1098 HSSTROL3_TI0 882 1098 HSSTROL3_TIl 974 1190 HSSTROL3_T12 834 1050 10 Segment cluster HSSTROL3_node_24 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T8 and HSSTROL3_T9. Table 23 below describes the starting and ending position of this segment on each transcript. 15 Table 23 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072050 PCT/IB2005/000433 503 HSSTROL3_T8 1099 1236 HSSTROL3_T9 1099 1236 Segment cluster HSSTROL3_node_25 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HSSTROL3_T8. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T8 1237 1536 10 Segment cluster HSSTROL3_node_26 according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3-T9 and HSSTROL3_T 11. Table 25 below describes the starting and ending position of this segment on each transcript. 15 Table 25 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 1099 1240 HSSTROL3_T8 1537 1678 HSSTROL3_T9 1237 1378 HSSTROL3T l 1191 1332 Segment cluster HSSTROL3_node_28 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can WO 2005/072050 PCT/IB2005/000433 504 be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T9 and HSSTROL3_T10. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 1357 2283 HSSTROL3_T9 1495 2421 HSSTROL3Tio 1215 2141 5 Segment cluster HSSTROL3_node_29 according to the present invention is supported by 109 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T 11 and HSSTROL3_T12. Table 27 below describes the 10 starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3 T5 2284 3194 HSSTROL3_T8 1795 2705 HSSTROL3_T9 2422 3332 HSSTROL3_T10 2142 3052 HSSTROL3_Ti 1 1449 2359 HSSTROL3_T12 1167 2077 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

WO 2005/072050 PCT/IB2005/000433 505 Segment cluster HSSTROL3_node_11 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, 5 HSSTROL3_T1O and HSSTROL3_Ti 1. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position endingpsto HSSTROL3_T5 314 361 HSSTROL3_T8 314 361 HSSTROL3_T9 314 361 HSSTROL3_T1O 314 361 HSSTROL3TI 314 361 10 Segment cluster HSSTROL3_node_17 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3-T5, HSSTROL3-T8, HSSTROL3_T9, HSSTROL3_T10, HSSTROL3_T1I1 and HSSTROL3_T12. Table 29 below describes the starting and ending position of this segment on each transcript. 15 Table 29 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3 T5 640 680 HSSTROL3_T8 640 680 HSSTROL3_T9 640 680 HSSTROL3_TI0 640 680 HSSTROL3_TI 1 640 680 WO 2005/072050 PCT/IB2005/000433 506 HSSTROL3_T12 592 632 Segment cluster HSSTROL3_node-18 according to the present invention can be found in the following transcript(s): HSSTROL3_T5, HSSTROL3-T8, HSSTROL3_T9, 5 HSSTROL3_T1O, HSSTROL3_Ti 1 and HSSTROL3_12. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 681 698 HSSTROL3_T8 681 698 HSSTROL3_T9 681 698 HSSTROL3_TI0 681 698 HSSTROL3_TIl 681 698 HSSTROL3_12 633 650 10 Segment cluster HSSTROL3-node_20 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_11. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T11 882 973 15 Segment cluster HSSTROL3_node_27 according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can WO 2005/072050 PCT/IB2005/000433 507 be found in the following transcript(s): HSSTROL3_T5, HSSTROL3_T8, HSSTROL3_T9, HSSTROL3T10, HSSTROL3_T 1I and HSSTROL3_T12. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSSTROL3_T5 1241 1356 HSSTROL3_TS 1679 1794 HSSTROL3_T9 1379 1494 HSSTROL3_T1O 1099 1214 HSSTROL3_Tl1 1333 1448 HSSTROL3_T12 1051 1166 5 10 Variant protein alignment to the previously known protein: Sequence name: MM11_HUMAN Sequence documentation: 15 Alignment of: HSSTROL3_P4 x MM11_HUMAN Alignment segment 1/1: Quality: 4444.00 20 Escore: 0 Matching length: 445 Total length: 445 WO 2005/072050 PCT/IB2005/000433 508 Matching Percent Similarity: 99.78 Matching Percent Identity: 99.78 Total Percent Similarity: 99.78 Total Percent Identity: 99.78 5 Gaps: 0 Alignment: 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 1 0 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 1111111|1 I 111111111 1111| 1 |11 llllllllllllllll I 15 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 lillllllllllllllllllllllllllllllllllllllllllllllll 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 20 . . 151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 25 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 |||| | 1| |1 111 II11111111111| 1 ||llllll ll l l llll l l llII 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 3 0 1 1l l l 1l l l i l l l i l l l i l i l l l l l1 l l l l i l l l l l l l l l l l l l 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 WO 2005/072050 PCT/IB2005/000433 509 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 1 1 l l l l l l l l l l l l l l l l l l l l l l ll l l l l l l l ll l l l l l l l l l l l l l 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 5 351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400 351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400 10 401 YFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG 445 l i l l l 1 ll l l l ll l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i I 401 YFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG 445 15 Sequence name: MM11_HUMAN 20 Sequence documentation: Alignment of: HSSTROL3_P5 x MM11_HUMAN 25 Alignment segment 1/1: Quality: 3566.00 Escore: 0 Matching length: 358 Total 30 length: 358 WO 2005/072050 PCT/IB2005/000433 510 Matching Percent Similarity: 99.72 Matching Percent Identity: 99.72 Total Percent Similarity: 99.72 Total Percent Identity: 99.72 5 Gaps: 0 Alignment: 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 10 llll 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLAPALPPDVHHLHAERRGPQP 50 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 1 1 1 1 1 11 1 1 1 1 1 1 1III11 | | | 1 111 | | | | 11 | l ll l l l l l l l l l l l l l l lI 15 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 20 - - 151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 l i l l l l l l l ll ii l l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 25 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 WO 2005/072050 PCT/IB2005/000433 511 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 5 351 QGHIWFFQ 358 351 QGHIWFFQ 358 10 15 Sequence name: MM11_HUMAN Sequence documentation: Alignment of: HSSTROL3_P7 x MM11 HUMAN 20 Alignment segment 1/1: Quality: 3575.00 Escore: 0 25 Matching length: 359 Total length: 359 Matching Percent Similarity: 99.72 Matching Percent Identity: 99.72 Total Percent Similarity: 99.72 Total Percent 30 Identity: 99.72 Gaps: 0 WO 2005/072050 PCT/IB2005/000433 512 Alignment: 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP .50 5 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 l i l l l l l l l l l l l l l l l l l l l l l l l l l l | | | | | 1 | | | ||11 1 | |I 10 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 15 151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 11||1111|111 lillllllllllllllllllllllllllllllllli1 151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 20 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 |||1 1 | II11|||||||||| 11 1| 11 1||1 ||1 | 11| 11 |1 |||1 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 25 1 1 l l l1 l lil1 l l l l | | | | | 1 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASPRHWQGLPSPVDAAFEDA 350 30 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 WO 2005/072050 PCT/IB2005/000433 513 351 QGHIWFFQG 359 111111||| 351 QGHIWFFQG 359 5 10 Sequence name: MM11_HUMAN Sequence documentation: Alignment of: HSSTROL3_PB x MM11_HUMAN 15 Alignment segment 1/1: Quality: 2838.00 Escore: 0 20 Matching length: 286 Total length: 286 Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65 Total Percent Similarity: 99.65 Total Percent 25 Identity: 99.65 Gaps: 0 Alignment: 30 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 1l 1l l l l l 11l 1l l l ll l ll l 11ll l ll l l l l l l l l l l ll l l l l l l ll l l li WO 2005/072050 PCT/IB2005/000433 514 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 I l 1 l||||||||||||||| I 1l l 111||| l11l I I1||||| 1||||| I 5 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 |||1 |I 1 l l1l1 l1l 1||||1 | ||||||1 1|1 11 I I | 1| 1 || 1 I I I 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 10 151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 |1 I|||||||11 lIiI 1|||1I11 l| | || i|| 1| | |1 |111 I 151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 15 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286 20 11|||| 111|||1|| | | 1||11 1 |||| 1 I I ll I 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286 25 Sequence name: MM11_HUMAN 30 Sequence documentation: WO 2005/072050 PCT/IB2005/000433 515 Alignment of: HSSTROL3_P9 x MM11_HUMAN Alignment segment 1/1: 5 Quality: 3316.00 Escore: 0 Matching length: 343 Total length: 359 Matching Percent Similarity: 99.71 Matching Percent 10 Identity: 99.71 Total Percent Similarity: 95.26 Total Percent Identity: 95.26 Gaps: 1 15 Alignment: 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 I I| | 1 | I| | || | | | | | | | | | | | | |I li i I 11 1l I l I l | | | | | 1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50 20 . - 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK. ... 96 ||||I l l l l l 1 l lI | | 1|||1 l1|| | | 1 |1| 1 ||I 11 51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100 25 97 .............. RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 134 | | | | | | 1 | | 1 | 1 I i | | | | | I l l | | l I l I l1 l1i I1l1 101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150 135 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 184 30 11111111 | |||11 |||||||1 ||1 |||11 ||||I ||11|| 151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200 WO 2005/072050 PCT/IB2005/000433 516 185 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 234 201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250 5 . 235 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 284 l 11ll l ill II 1 1 I I 1 11ll l l l l l l l l l l l 11 llllllllllllllll 251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300 10 285 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 334 |I lllllllllllllll111 1 I 1 11llll 1Illll 1 Ill Il iil| 301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350 335 QGHIWFFQG 343 15 I I I I I | | | | 351 QGHIWFFQG 359 Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP-11) 20 (ST3) SL-3 HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 in normal and cancerous breast tissues Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) (SL-3 transcripts detectable by or according to seg24 HSSTROL3 seg24 amplicon(s) and HSSTROL3 seg24F and HSSTROL3 seg24R primers was measured by real 25 time PCR. In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon) SDHA (GenBank Accession No. NM_004168; amplicon SDHA-amplicon) and G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized 30 to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem WO 2005/072050 PCT/IB2005/000433 517 (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative b median of the normal PM samples. Figure 29A is a histogram showing over expression of the above-indicated Stromelysin 5 3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MIMP- 11) (ST3) (SL-3) transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. As is evident from Figure 29A, the expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MM\[P- 11) (ST3) (SL-3) transcripts detectable by the above 10 amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos.56-60, 63-67 Table 1, "Tissue samples in testing panel"). Notably an over expression of at least 5 fold was found in 20 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. 15 The P value for the difference in the expression levels of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) (SLr3) transcripts detectable by the above amplicon(s) in Breast cancer samples versus the normal tissue samples was determined by T test as 6.46E-03.

WO 2005/072050 PCT/IB2005/000433 518 Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.12E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following 5 primer pair was used as a non- limiting illustrative example only of a suitable primer pair: HSSTROL3 seg24F forward primer; and HSSTROL3 seg24R reverse primer.The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: HSSTROL3 seg24. 10 HSSTROL3 seg24 Forward Primer (SEQ ID NO:867): ATTTCCATCCTCAACTGGCAGA HSSTROL3 seg24 Reverse Primer (SEQ ID NO:868): TGCCCTGGAACCCACG HSSTROL3 seg24 Amplicon (SEQ ID NO: 869): ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCCAGGGAC 15 TTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAGGGCA Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) (SL-3)HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 in different normal tissues 20 Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP- 11) (ST3) (SL-3) transcripts detectable by or according to HSSTROL3 seg24 amplicon(s) and HSSTROL3 seg24F and HSSTROL3 seg24R was measured by real time PCR. In parallel the expression of four housekeeping genes UBC (GenBank Accession No. 25 BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), RPL19 (GenBank Accession No. NM_00098 1; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each 30 RT sample was then divided by the median of the quantities of the lung samples (sample Nos.

WO 2005/072050 PCT/IB2005/000433 519 15-17 Table 2,"Tissue samples on normal panel" above), to obtain a value of relative expression of each sample relative to median of the lung samples. Primers and amplicon are as above. The results are presented in Figure 29B, demonstrating the expression of Stromelysin-3 5 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) (SL-3) HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24, in different normal tissues. Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMIP- 11) 10 (ST3) (SL-3) HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 junc20-21 in normal and cancerous breast tissues Expression of Stromelysin-3 precursor transcripts detectable by or according to junc20 21, HSSTROL3junc2O-21 amplicon(s) and primers HSSTROL3junc2O-21F and HSSTROL3junc2O-21R was measured by real time PCR. It should be noted that for this 15 experiment, RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 19801, USA, www.absbioreagents.com), GOG for ovary samples- Pediatic Cooperative Human Tissue Network, Gynecologic Oncology Group Tissue Bank, Children Hospital of Columbus (Columbus OH 43205 USA) or Ambion (Austin, TX 78744 USA, 20 www.ambion.com).Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion). In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. 25 BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of 30 each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to WO 2005/072050 PCT/IB2005/000433 520 obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 30A is a histogram showing over expression of the above-indicated Stromelysin 3 precursor transcripts in cancerous breast samples relative to the normal samples. 5 As is evident from Figure 30A, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non cancerous samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above). Notably an over-expression of at least 5 fold was found in 13 out of 28 adenocarcinoma samples. 10 Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 1.28F-02. 15 Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples wth P value of 4.26E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non 20 limiting illustrative example only of a suitable primer pair: HSSTROL junc20-2 1 F forward primer; and HSSTROL junc20-21R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: HSSTROL 25 junc20-21. Forward primer HSSTROL junc20-21F (SEQ ID NO:870): TCTGCTGGCCACTGTGACTG Reverse primer HSSTROL junc20-21R (SEQ ID NO:871): GAAGAAAAAGAGCTCGCCTCG 30 Amplicon HSSTROL junc20-21 (SEQ ID NO:872):

TCTGCTGGCCACTGTGACTGCAGCATATGCCCTCAGCATGTGTCCCTCTCTCCCACC

WO 2005/072050 PCT/IB2005/000433 521 CCAGCCAGACGCCCCGCCAGATGCCTGTGAGGCCTCCTTTGACGCGGTCTCCACCA TCCGAGGCGAGCTCTTTTTCTTC Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) 5 (ST3) (SI-3) HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 junc21-27 in normal and cancerous breast tissues Expression of Stromelysin-3 precursor transcripts detectable by or according to junc2l-27, HSSTROL3junc2l-27 amplicon(s) and primers HSSTROL3junc21-27F and HSSTROL3junc21-27R was measured by real time PCR (RNA was as for the experiment 10 above). In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon SDHA-amplicon), G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized 15 to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. 20 Figure 30B is a histogram showing over expression of the above-indicated Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples . As is evident from Figure 30B, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non cancerous samples (Sample Nos. 56-60, 63-67 Table 1: Tissue samples in testing panel, above). 25 Notably an over-expression of at least 20 fold was found in 20 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of Stromelysin-3 precursor 30 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 5.98E-03.

WO 2005/072050 PCT/IB2005/000433 522 Threshold of 20 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.66F-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present 5 invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: HSSTROL junc21-27F forward primer; and HSSTROL junc2l-27R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon 10 was obtained as a non- limiting illustrative example only of a suitable amplicon: HSSTROL junc2l-27. Forward primer HSSTROL junc2l-27F (SEQ ID NO:873): ACATTTGGTTCTTCCAAGGGACTAC Reverse primer HSSTROL junc2l-27R (SEQ ID NO:874): 15 TCGATCTCAGAGGGCACCC Amplicon HSSTROL junc2l-27 (SEQ ID NO:875): ACATTTGGTTCTTCCAAGGGACTACTGGCGTTTCCACCCCAGCACCCGGCGT GTAGACAGTCCCGTGCCCCGCAGGGCCACTGACTGGAGAGGGGTGCCCTCTGAGAT CGA 20 Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase- 11) (MMP- 11) (ST3) (SL-3) HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg25 in normal and cancerous breast tissues Expression of Stromelysin-3 precursor transcripts detectable by or according to seg25, 25 HSSTROL3 junc2l-27 amplicon(s) and primers HSSTROL3junc2J-27F and HSSTROL3junc2l 27R was measured by real time PCR (RNA was as for the experiment above). In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1 amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), G6PD 30 (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the WO 2005/072050 PCT/IB2005/000433 523 quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up regulation for each sample relative to median of the normal PM samples. 5 Figure 30C is a histogram showing over expression of the above-indicated Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples . As is evident from Figure 30C, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non cancerous samples (Sample Nos. 56-60, 63-67 Table 1: Tissue samples in testing panel, above). 10 Notably an over-expression of at least 5 fold was found in 20 out of 28 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of Stromelysin-3 precursor 15 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 5.79F-02. Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.75E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

WO 2005/072050 PCT/IB2005/000433 524 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: HSSTROL seg25F forward primer; and HSSTROL seg25R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: HSSTROL seg25. Forward primer HSSTROL seg25F (SEQ ID NO:876): CACTGCCCCAGCTTATCCC 10 Reverse primer HSSTROL seg25R (SEQ ID NO:877): CTCTCCCAGCCTCAGTTTCCT Amplicon HSSTROL seg25 (SEQ ID NO:878): CACTGCCCCAGCTTATCCCAGGCCTCCCGCTTCCCTCTGCGGGTGGGGTGCTGAGCA GGCATTATTGGCCTGCATGTTTTACTGATGAGGAAACTGAGGCTGGGAGAG 15 DESCRIPTION FOR CLUSTER AY180924 Cluster AY 180924 features 1 transcript(s) and 3 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 20 Table ] - Transcripts of interest Transcrpt Name Sequence ID No. AY180924_PEA_1 Ti 276 Table 2 - Segments of interest Segment Name Sequence ID No. AYI80924_PEA 1 node 3 277 AYI80924_PEAI node 0 278 AYl80924_PEA 1_node_2 279 WO 2005/072050 PCT/IB2005/000433 525 Table 3 - Proteins of interest Protein Name Sequence ID No. AY180924_PEA_1 P3 281 These sequences are variants of the known protein Latherin precursor (SwissProt accession identifier LATHHUMAN; known also according to the synonyms Breast cancer and 5 salivary gland expressed protein), SEQ ID NO: 280, referred to herein as the previously known protein. Protein Latherin precursor is known or believed to have the following function(s): surfactant properties. The sequence for protein Latherin precursor is given at the end of the application, as "Latherin precursor amino acid sequence". The protein Latherin localization is 10 believed to be Secreted. As noted above, cluster AY 180924 features 1 transcript, which were listed in Table 1 above. This transcript encode for protein which is a variant of protein Latherin precursor. A description of the variant protein according to the present invention is now provided. 15 Variant protein AY180924_PEA_1_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AY180924_PEA_1_Ti. An alignment is given to the known protein (Latherin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 20 variant protein according to tle present invention to each such aligned protein is as follows: Comparison report between AY 180924_PEA_1_P3 and LATHHUMAN: 1.An isolated chimeric polypeptide encoding for AY180924_PEA_1-P3, comprising a first amino acid sequence being at least 90 % homologous to MILNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN corresponding to amino acids 1 - 33 of 25 LATHHUMAN, which also corresponds to amino acids 1 - 33 of AYI80924_PEA_1_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY WO 2005/072050 PCT/IB2005/000433 526 corresponding to amino acids 34 - 64 of AY180924_PEA_1_P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of AY180924_PEA_1_P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95 % homologous to the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY in AY 180924_PEA_1_P3. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein AYI80924_PEA_-_P3 is encoded by the following transcript(s): 15 AY180924-PEA-1-Tl, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AY 180924-PEA_1_TI is shown in bold; this coding portion starts at position 73 and ends at position 264. The transcript also has the following SNPs as listed in Table 4 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 20 known SNPs in variant protein AY180924_PEAlP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 4 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 361 C ->T Yes 459 C->A Yes As noted above, cluster AY180924 features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) 25 are portions of nucleic acid sequence(s) which are described herein separately because they are WO 2005/072050 PCT/IB2005/000433 527 of particular interest. A description of each segment according to the present invention is now provided. Segment cluster AY180924_PEA_1_node_3 according to the present invention is 5 supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AY180924_PEA_1_Ti. Table 5 below describes the starting and ending position of this segment on each transcript. Table 5 - Segment location on transcripts Transcript name Segment starting position Segment ending position AY180924_PEA_1_TI 173 657 According to an optional embodiment of the present invention, short segments related to 10 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster AY180924_PEA_1_node_0 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This 15 segment can be found in the following transcript(s): AY180924_PEA_1_Ti. Table 6 below describes the starting and ending position of this segment on each transcript. Table 6 - Segment location on transcripts Transcript name Segment starting position Segment ending position AY180924_PEA_1-TI 1 58 20 Segment cluster AY180924_PEA_1_node_2 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AY180924_PEA_1_Ti. Table 7 below describes the starting and ending position of this segment on each transcript. Table 7 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072050 PCT/IB2005/000433 528 AY180924_PEA_1_Ti 59 f72 Variant protein alignment to the previously known protein: Sequence name: /tmp/FepOCusBjG/YVh7Evl27H:LATHHUMAN 5 Sequence documentation: Alignment of: AY180924_PEA_1_P3 x LATHHUMAN 10 Alignment segment 1/1: Quality: 300.00 Escore: 0 Matching length: 33 Total 15 length: 33 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 20 Gaps: 0 Alignment: 1 MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN 33 2 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN 33 DESCRIPTION FOR CLUSTER R75793 WO 2005/072050 PCT/IB2005/000433 529 Cluster R75 793 features 3 transcript(s) and 9 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest TranscriptName Sequence ID No. R75793_PEA 1 TI 282 R75793_PEAIT3 283 R75793_PEA_1_T5 284 5 Table 2 - Segments of interest Segment Name Sequence ID No. R75793_PEA 1 node 0 285 R75793_PEA_1_node_9 286 R75793 PEA_1_node_11 287 R75793_PEA I node 14 288 R75793_PEA 1 node 4 289 R75793_PEA 1 node 5 290 R75793_PEA_1_node 6 291 R75793_PEA_1node 8 292 R75793_PEA 1 node 13 293 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) R75793_PEA_1_P2 295 R75793_PEA_1 TI R75793_PEA_1_P5 296 R75793_PEA_1_T5 R75793_PEAlP6 297 R75793_PEA_1_T3 10 Cluster R75793 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given WO 2005/072050 PCT/IB2005/000433 530 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 31 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 5 Overall, the following results were obtained as shown with regard to the histograms in Figure 31 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues. 10 Table 4 - Normal tissue distribution Name of Tissue Number epithelial 16 general 5 Breast 457 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 epithelial 3.3e-01 5.0e-01 9.2e-17 4.0 2.7e-07 2.0 general 1.3e-0l 2.0e-01 3.4e-33 8.0 2.0e-17 3.9 Breast 5.9e-01 7.le-01 1.2e-07 2.1 1.4e-02 1.0 15 As noted above, cluster R75793 features 3 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. Variant protein R75793_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 20 R75793_PEA_1_Ti. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 531 Comparison report between R75793_PEA_1_P2 and Q96DR8 (SEQ ID NO: 294): 1.An isolated chimeric polypeptide encoding for R75793_PEA-lP2, comprising a first amino acid sequence being at least 90 % homologous to MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAATTATTAAPT 5 TATTAASTTARKDIP corresponding to amino acids 1 - 74 of Q96DR8, which also corresponds to amino acids 1 - 74 of R75793_PEAlP2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AP corresponding to amino acids 75 - 76 of R75793_PEA_1_P2, wherein said first amino acid 10 sequence and second amino acid sequence are contiguous and in a sequential order. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 15 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein R75793_PEAl-P2 is encoded by the following transcript(s): 20 R75793_PEA_1_TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA_1-TI is shown in bold; this coding portion starts at position 69 and ends at position 296. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 25 known SNPs in variant protein R75793_PEAlP2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 15 C ->A Yes WO 2005/072050 PCT/IB2005/000433 532 59 G->T Yes 179 T->C No 179 T->G No 227 G->A Yes 516 A->T No Variant protein R75793_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 R75793_PEA_1_T5. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither 10 trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein R75793-PEA_1_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last colunm indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 54 H -> R Yes 20 Variant protein R75793_PEAl_P5 is encoded by the following transcript(s): R75793_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA_1_T5 is shown in bold; this coding portion starts at WO 2005/072050 PCT/IB2005/000433 533 position 69 and ends at position 383. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEAlP5 sequence provides support for the deduced 5 sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 15 C ->A Yes 59 G ->T Yes 229 A ->G Yes Variant protein R75793_PEA_1_P6 according to the present invention has an amino acid 10 sequence as given at the end of the application; it is encoded by transcript(s) R75793_PEAIT3. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both 15 signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein R75793_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the 20 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793-PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 534 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 16 R->Q Yes Variant protein R75793-PEA_1_P6 is encoded by the following transcript(s): R75793-PEA_1_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA-_IT3 is shown in bold; this coding portion starts at 5 position 329 and ends at position 502. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA-1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 10 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 327 T-> C No 327 T-> G No 375 G-> A Yes 635 A -> T No As noted above, cluster R75793 features 9 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 15 provided. Segment cluster R75793_PEA_1_node_0 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA_1_T3. Table 11 below describes the 20 starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 535 Transcript name Segment Segment starting position ending position R75793_PEA_1_T3 1 274 Segment cluster R75793_PEA_1_node_9 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R75793_PEA_1_T5. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793_PEAI T5 169 491 10 Segment cluster R75793_PEA_1_node_11 according to the present invention is supported by 59 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793-PEA_1_T1 and R75793_PEAIT3. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793_PEA_1 TI 169 291 R75793_PEA1 _T3 317 439 15 Segment cluster R75793_PEA_1_node_14 according to the present invention is supported by 41 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 536 can be found in the following transcript(s): R75793_PEA_1_TI and R75793_PEA_1_T3. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment Segment starting position ending position. R75793_PEA_1_Ti 321 527 R75793_PEA_1_T3 440 646 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster R75793_PEA_1_node_4 according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): R75793-PEA_1_TI and R75793_PEA_1_T5. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793-PEA_1_TI 1 41 R75793_PEAIT5 1 4 15 Segment cluster R75793-PEA-lnode_5 according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA-1_TI and R75793_PEA__T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072050 PCT/IB2005/000433 537 R75793_PEA1_TI 42 74 R75793 PEA 1 T5 42 74 Segment cluster R75793_PEA_-node_6 according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R75793-PEA_1_TI and R75793_PEAIT5. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793_PEA_1_TI 75 126 R75793_PEA_1 T5 75 126 10 Segment cluster R75793_PEA _1node_8 according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA_1_Tl, R75793_PEA_1-T3 and R75793-PEA_1_T5. Table 18 below describes the starting and ending position of this segment on each transcript. 15 Table 18 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793_PEA_1 Ti 127 168 R75793_PEA_1_T3 275 316 R75793_PEA_1_T5 127 168 Segment cluster R75793_PEA_1_node_13 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 538 can be found in the following transcript(s): R75793_PEA_1_Ti. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position R75793_PEA_1_TI 292 320 5 Variant protein alignment to the previously known protein: Sequence name: Q96DR8 10 Sequence documentation: Alignment of: R75793 PEA 1 P2 x Q96DR8 Alignment segment 1/1: 15 Quality: 681.00 Escore: 0 Matching length: 74 Total length: 74 20 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: WO 2005/072050 PCT/IB2005/000433 539 1 MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAA 50 li l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l1 1 1ll l l l l l l l iI 1 MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAA 50 5 51 TTATTAAPTTATTAASTTARKDIP 74 51 TTATTAAPTTATTAASTTARKDIP 74 10 Expression of Homo sapiens small breast epithelial mucin (LOC 118430) R75793 transcripts which are detectable by amplicon as depicted in sequence name R75793 junc1 1-13 in normal and cancerous Breast tissues Expression of Homo sapiens small breast epithelial mucin (LOC118430) transcripts detectable by or according to juncl1-13, R75793 juncll-13 amplicon(s) and primers R75793 15 junc11-13F and R75793 junc11-13R was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) and G6PD (GenBank Accession No. NM_000402; G6PD amplicon), was measured similarly. For each RT 20 sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples. 25 In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a failure of this particular experiment.

WO 2005/072050 PCT/IB2005/000433 540 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: R75793 junc1 1- 13F forward primer; and R75793 junc11- 13R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R75793 junc1 1 13. Forward primer R75793 junc 1-13F (SEQ ID NO:879): 10 TGATGATGAAGCCCCTGATG Reverse primer R75793 junc1 1-13R (SEQ ID NO:880): TATTGTCAAGGGGCTGGAATGT Amplicon R75793 juncl1-13 (SEQ ID NO:881): TGATGATGAAGCCCCTGATGCTGAAACCAC TGCTGCTGCAACCACTGCGACCACTG 15 CTGCTCCTACCACTGCAACCACCGCTGCTTCTACCACTGCTCGTAAAGACATTCCAG CCCCTTGACAATA Expression of Homo sapiens small breast epithelial mucin (LOC 18430) R75793 transcripts which are detectable by amplicon as depicted in sequence name R75793 seg9 in normal and 20 cancerous Breast tissues Expression of Homo sapiens small breast epithelial mucin (LOC118430) transcripts detectable by or according to seg9, R75793seg9 amplicon(s) and primers R75793 seg9F and R75793seg9R was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRT1 25 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) and G6PD (GenBank Accession No. NM_000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the 30 quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue WO 2005/072050 PCT/IB2005/000433 541 samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples. In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a failure 5 of this particular experiment. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: R75793seg9F forward primer; and R75793seg9R reverse primer. 10 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R75793seg9. Forward primer R75793seg9F (SEQ ID NO:882): TCCAGCAATAACCATTTTTCACTTC 15 Reverse primer R75793seg9R (SEQ ID NO:883): GCTTTCACAGACTTTTGCTTAGGATT Amplicon R75793seg9 (SEQ ID NO:884): TCCAGCAATAACCATTTTTCACTTCCAGCCTCATGTCAAACAGCCAGTTTCCATGTG GATAGTCTTTGTTATAAGGAATCCTAAGCAAAAGTCTGTGAAAGC 20 DESCRIPTION FOR CLUSTER HUMCAIXIA Cluster HUMCA1XIA features 4 transcript(s) and 46 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 25 Table 1 - Transcripts of interest Transcript Name Sequence ID No. HUMCA1XIA _T16 298 HUMCA1XIA_T17 299 HUMCA1XIA_T19 300 HUMCA1XIAT20 301 WO 2005/072050 PCT/IB2005/000433 542 Table 2 - Segments of interest Segment Name Sequence ID No. HUMCAlXIA node 0 302 HLUMCAIXIA node 2 303 H-UMCAIXIA node 4 304 HUMCAIXIA node 6 305 HIUMCA1XIA node 8 306 HUMCA1XIA node 9 307 HUvICAIXIA node_18 308 HUMCA1XIA node 54 309 HUMCAIXIA node 55 310 HTMCA 1XIAnode_92 311 HUMCAIXIA node11 312 HUMCA1XIA node 15 313 HIJUMCA1lXIAnode_19 314 HUJMCA1XIAnode_21 315 HUMCA1XIA node_23 316 HUMCAIXIAnode_25 317 HU-RMCAIXIAnode_27 318 IUMCAIXIAnode_29 319 HUMCA1XIA node_31 320 HUMCAIXIA node 33 321 H-JUMCAIXIA node 35 322 HUMCAIXIA_node_37 323 HU-JMCA1XIA node_39 324 HUMI\CA1XIAnode_41 325 HIJMCA1XIAnode_43 326 HUMCA1XIA-node_45 327 WO 2005/072050 PCT/IB2005/000433 543 HUIMCAIXIA node 47 328 HUMCA1XIA node_49 329 HUMCA1XIA-node_51 330 HUMCAIXIA node_57 331 HUIMCA1XIA node_59 332 HUMCA1XIAnode_62 333 HLJMCA1XIAnode_64 334 HUIMCA1XIA node_66 335 HUMCA1XIA node_68 336 HU-JMCAIXIA node 70 337 HUMCA1XIA-node_72 338 HUMCA1XIAnode_74 339 HUMCA1XIA node 76 340 HUMCA1XIA-node_78 341 H-LUMCAIXIA node 81 342 HUMCAIXIA-node_83 343 HUTMCA1XIA node-85 344 HIUMCA1XIAnode_87 345 HUMCA1XIAnode_89 346 HUMCAIXIA node_91 347 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) HUIMCAIXIAP14 350 HUMCA1XIAT16 HUMCAIXIAP15 351 HUMCAIXIA_T17 HJMCAlXIAP16 352 HUMCAIXIA T19 HUMCAlXIAP17 353 HUMCA1XIAT20 WO 2005/072050 PCT/IB2005/000433 544 These sequences are variants of the known protein Collagen alpha 1 (SwissProt accession identifier CAIB_HUJMAN; known also according to the synonyms XI), SEQ ID NO:348, referred to herein as the previously known protein. Protein Collagen alpha 1 is known or believed to have the following function(s): May 5 play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils. The sequence for protein Collagen alpha 1 is given at the end of the application, as "Collagen alpha 1 amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 625 G -> V (in STL2). /FTId=VAR 013583. 676 G -> R (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR_013584. 921 - 926 Missing (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR_013585. 1313- 1315 Missing (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR_013586. 1516 G -> V (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR_013587. 941 - 944 KDGL -> RMGC 986 Y ->H 1074 R ->P 1142 G->D 1218 M -> W 1758 T-> A 1786 S -> N 10 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cartilage condensation; vision; hearing; cell-cell adhesion; extracellular matrix organization and biogenesis, which are annotation(s) related to Biological WO 2005/072050 PCT/IB2005/000433 545 Process; extracellular matrix structural protein; extracellular matrix protein, adhesive, which are annotation(s) related to Molecular Function; and extracellular matrix; collagen; collagen type XI, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl 5 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HUMCAIXIA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 10 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 32 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 15 Overall, the following results were obtained as shown with regard to the histograms in Figure 32 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors. 20 Table 5 - Normal tissue distribution Name of Tissue Number Adrenal 0 Bone 207 Brain 13 Colon 0 epithelial I1 general I I head and neck 0 kidney 0 Lung 0 WO 2005/072050 PCT/IB2005/000433 546 Breast 8 pancreas 0 stomach 73 Uterus 9 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPi R3 SP2 R4 adrenal 4.2e-01 1.9e-Ol 9.6e-02 3.4 8.2e-02 3.6 Bone 2.4e-01 6.3e-O1 7.7e-10 4.3 5.3e-03 1.6 Brain 5.0e-01 6.9e-O 1.Se-01 2.1 4.2e-01 1.3 Colon 1.3e-02 2.9e-02 2.4e-01 3.0 3.5e-01 2.4 epithelial 3.9e-04 3.2e-03 1.3e-03 2.3 1.8e-02 1.7 general 5.6e-05 1.6e-03 9.5e-17 4.5 L.le-09 2.8 head and neck 1.2e-01 2.le-01 1 1.3 1 1.1 kidney 6.5e-01 7.2e-01 3.4e-01 2.4 4.9e-01 1.9 Lung 5.3e-02 9.le-02 5.5e-05 7.3 5.0e-03 4.0 Breast 4.3e-0l 5.6e-01 6.9e-01 1.4 8.2e-01 1.1 pancreas 3.3e-01 1.8e-01 4.2e-01 2.4 1.5e-01 3.7 stomach 5.0e-0l 6.le-01 6.9e-01 1.0 6.7e-01 0.8 Uterus 7.le-01 7.0e-01 6.6e-01 1.1 6.4e-01 1.1 As noted above, cluster IIUMCA 1 XIA features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Collagen alpha 5 1. A description of each variant protein according to the present invention is now provided. Variant protein HUMCAIXIA_P14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCAIXIA_T16. An alignment is given to the known protein (Collagen alpha 1) at the end 10 of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 547 Comparison report between HUMCA1XIA_P14 and CA1BHUMANV5 (SEQ ID NO: 349): 1.An isolated chimeric polypeptide encoding for H{UMCA1XIAP14, comprising a first amino acid sequence being at least 90 % homologous to 5 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT 10 EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP 15 GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVK GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR 20 GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1 - 1056 of CAIB-HUMAN_V5, which also corresponds to amino acids 1 - 1056 of HUMCALXIAP14, and a second amino acid sequence being at least 25 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLMEL corresponding to amino acids 1057 - 1081 of HUMCA1XIAP14, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 30 2.An isolated polypeptide encoding for a tail of HUMCA1XIAP14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 548 more preferably at least about 90% and most preferably at least about 95% honologous to the sequence VSMMIINSQTIMVVNYSSSFITLML in HJMCA1XIA_P14. It should be noted that the known protein sequence (CA lB_IHTMAN; SEQ ID NO:348) 5 has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CAIB_HUMANV5 (SEQ ID NO:349). These changes were previously known to occur and are listed in the table below. Table 7 - Changes to CAIB_HUMAN_V5 SNP position(s) on Type of change amino acid sequence 987 conflict 10 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 15 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HJMCA1XIAP14 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 20 the SNP is known or not; the presence of known SNPs in variant protein HUMCAIXIA_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 8 W -> G Yes WO 2005/072050 PCT/IB2005/000433 549 46 D->E Yes 559 G->S Yes 832 G-> * Yes 986 H-> Y Yes 1061 I->M Yes 1070 V->A Yes Variant protein HIUMCA IXIAP14 is encoded by the following transcript(s): HUMCA1XIA_T16, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCAIXIA_T16 is shown in bold; this coding portion starts at 5 position 319 and ends at position 3561. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last colunm indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A-> G No 241 T->A Yes 340 T-> G Yes 456 T-> G Yes 1993 G-> A Yes 2812 G->T Yes 3274 C -> T Yes 3282 C -> T Yes 3501 A -> G Yes 3527 T-> C Yes WO 2005/072050 PCT/IB2005/000433 550 ' Variant protein HULJMCA1XIAP15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T17. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein 5 sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCA1XIAP15 and CAIBHUMAN: 1.An isolated chimeric polypeptide encoding for HUMCA1XIAP 15, comprising a first amino acid sequence being at least 90 % homologous to 10 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT 15 EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEF GPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP 20 GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1 - 714 of CAiBHUMAN, which also corresponds to amino acids 1 - 714 of HUMCA1XIAP15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 25 preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK corresponding to amino acids 715 - 729 of HUMCA1XIAP15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMCA1XIA_P15, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 551 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFG[LIPLQK in HUMCAIXIA_P15. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signalpeptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HUMCAIXIA-P15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCAIXIA_P15 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino a~d(s) Previously known SNP? sequence 8 W -> G Yes 46 D ->E Yes 559 G ->S Yes The glycosylation sites of variant protein HUMCAlXIAP 15, as compared to the known protein Collagen alpha 1, are described in Table 11 (given according to their position(s) on the 20 amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last colunm indicates whether the position is different on the variant protein). Table 11 - Glycosylation sites) WO 2005/072050 PCT/IB2005/000433 552 Position(s) on known amino Present in variant protein? acid sequence 1640 no Variant protein HUMCA1XIA-P15 is encoded by the following transcript(s): HUMCA1XIAT17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUJMCA1XIA_T17 is shown in bold; this coding portion starts at 5 position 319 and ends at position 2505. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCAIXIAP15 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A ->G No 241 T-> A Yes 340 T->G Yes 456 T-> G Yes 1993 G->A Yes 2473 C -> T Yes Variant protein HLUMCA1XIAP16 according to the present invention has an amino acid sequence as given at tle end of the application; it is encoded by transcript(s) 15 HUIMCA1XIAT19. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCA1XIA_P16 and CAIB_[HUMAN: WO 2005/072050 PCT/IB2005/000433 553 1.An isolated chimeric polypeptide encoding for HUMCA1XIA-P16, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY 5 NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSlN 10 GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1 - 648 of CAIB_HUMAN, which also corresponds to amino 15 acids 1 - 648 of HUMCA1XIAP16, a second amino acid sequence being at least 90 % homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667 - 714 of CA1BHUMAN, which also corresponds to amino acids 649 - 696 of HUMCA1XIA-P16, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE corresponding to amino acids 697 - 738 of HUMCA1XIA_P16, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of I-RJMCA1XIA_P16, 25 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and 30 ending at any of amino acid numbers 649+ ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072050 PCT/IB2005/000433 554 3.An isolated polypeptide encoding for a tail of HUMCA1XIAP16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE in 5 HUMCA1XIAP16. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 10 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMCAlXIA_P16 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the 15 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCALXIAP16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations SNP position(s) on amino acid, Alternative am~ino acid(s.) Previously known SNP? sequence 8 W->G Yes 46 D -> E Yes 559 G -> S Yes 20 The glycosylation sites of variant protein HUMCA IXIAP16, as compared to the known protein Collagen alpha 1, are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is 25 different on the variant protein).

WO 2005/072050 PCT/IB2005/000433 555 Tabe 14 - Glycosylation site(s) Po!ion(s) on known amino Present in variant protein? acidq" sequence 1640 no Variant protein HUMCA1XIA_P16 is encoded by the following transcript(s): HUMCA1XIA_T19, for which the sequence(s) is/are given at the end of the application. The 5 coding portion of transcript HUMCA 1 XIAT 19 is shown in bold; this coding portion starts at position 319 and ends at position 2532. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCAIXIA_P16 sequence provides support for the deduced 10 sequence of this variant protein according to the present invention). Table 15 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A ->G No 241 T->A Yes 340 T->G Yes 456 T->G Yes 1993 G -> A Yes 2606 C -> A Yes 2677 T->G Yes 2849 C -> T Yes Variant protein HUMCAIXIA_P17 according to the present invention has an amino acid 15 sequence as given at the end of the application; it is encoded by transcript(s) HIUMCAlXIA_T20. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein WO 2005/072050 PCT/IB2005/000433 556 sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the presert invention to each such aligned protein is as follows: Comparison report between HUMCA1XIA_P17 and CAlB_HUMAN: 1.An isolated chimeric polypeptide encoding for HUMCA 1XIA_P 17, comprising a first 5 amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH 10 YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1 - 260 of CA1BHUMAN, which also corresponds to amino acids 1 - 260 of HUMCAlXIAP17, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ corresponding to amino acids 261 - 273 of HUMCA1XIA_P17, wherein 15 said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMCA1XIAP17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 20 sequence VRSTRPEKVFVFQ in HUMCA1XIA-P17. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans -membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMCA1XIA_P17 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the 30 amino, acid sequence, with the alternative amino acid(s) listed; the last colunm indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P17 WO 2005/072050 PCT/IB2005/000433 557 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 8 W ->G Yes 46 D ->E Yes 5 The glycosylation sites of variant protein HUMCAIXIAP17, as compared to the known protein Collagen alpha 1, are described in Table 17 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). 10 Table 17 - Glycosylation sites) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1640 no Variant protein HUMCA1XIA_P17 is encoded by the following transcript(s): HUMCA1XIAT20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIAT20 is shown in bold; this coding portion starts at 15 position 319 and ends at position 1137. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 1HJMCA1XIA_P17 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 18 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence, WO 2005/072050 PCT/IB2005/000433 558 157 A->G No 241 T->A Yes 340 T->G Yes 456 T->G Yes 1150 A->C Yes As noted above, cluster HULMCAlXIA features 46 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster H-UMCAlXIAnode_0 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HIMCAXIAT16, HUMCA1XIA_T17, 10 HUMCA1XIAT19 and HLJMCAlXIA_T20. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 1 424 HUMCA1XIA_T17 1 424 HLMCA1XIA-T19 1 424 HUMCA1XIAT20 1 424 15 Segment cluster IUMCA1XI A_node_2 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, H-UMCA1XIA_T17, HJMCAlXIA_T19 and HU-JMCAlXIA-T20. Table 20 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 559 Table 20 - Segment location on transcripts Transcript'name Segment Segment starting position ending position HUMCA1XIAT16 425 592 HUMICA1IA T17 425 592 HJMCAlXIAT19 425 592 HJMCAlXIAT20 425 592 Segment cluster IUMCA XIA_node_4 according to the present invention is supported 5 by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16, IUMCAlXIAT17, HUMCAIXIA_T19 and HUMCAIXIAT20. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment Segment starting position ending position HULMCA I XIAT 16 593 806 IlTMCA IXIAT17 593 806 HUICA1XIAT19 593 806 HUMCA1XIA T20 593 806 10 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 22. 15 Table 22 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference HUMCA1XIA_0_18_0 breast malignant tumors BRS WO 2005/072050 PCT/IB2005/000433 560 Segment cluster HUMCA1XIA_node_6 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HU-MCAIXIAT16, HUMCA1XIAT17, HUMCAlXIA_T19 and HUMCA1XIA_T20. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 807 969 HUMCAlXIAT17 807 969 HUMCA1XIAT19 807 969 ITMCA1XIA_T20 807 969 10 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 24. Table 24 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference HLNiCAIXIA_0_18_0 breast malignant tumors BRS 15 Segment cluster HUMCAlXIA node_8 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA-T16, HUJMCAIXIA_T17, 20 IUMCAIXIA-T19 and HUMCA1XIAT20. Table 25 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 561 Table 25 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 970 1098 HUICA1XIAT17 970 1098 HIJMCAIXIAT19 970 1098 HUMCA1XIAT20 970 1098 Segment cluster HUMCAIXIAnode-9 according to the present invention is supported 5 by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA_T20. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIAT20 1099 1271 10 Segment cluster HUMCA 1 XIA-node 18 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16, HjMCAIXIA_T17 and HUMCA1XIA_T19. Table 27 below describes the starting and ending position of this segment 15 on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position ending position HJMCALXIA_T16 1309 1522 HUMCA1XIA_T17 1309 1522 WO 2005/072050 PCT/IB2005/000433 562 HUMCAXIA-T19 1309 1522 Segment cluster HUJMCA1XIAnode_54 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAXIAT19. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT19 2407 2836 10 Segment cluster HUMCA1XIAnode_55 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T17 and HUMCAlXIA_T19. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name, Segment Segment starting position ending position HIJMCA1XIAT17 2461 2648 HUMCAXAT19 2837 3475 15 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 30. 20 Table 30 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference WO 2005/072050 PCT/IB2005/000433 563 HUMCAlXIA_0-0_14909 breast malignant tumors BRS Segment cluster HUMCAlXIA node_92 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA_T16. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T16 3487 3615 10 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 15 Segment cluster HUMCA IXIAnode_ 11 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16, HUMCA1XIA_T17 and HUMCAIXIA_T19. Table 32 below describes the starting and ending position of this segment on each transcript. 20 Table 32 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIA_T16 1099 1215 HUMCA1XIA T17 1099 1215 HLJMCA1XIA_T19 1099 1215 WO 2005/072050 PCT/IB2005/000433 564 Segment cluster HUMCA1XIAnode_15 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, HUMCAIXIA_T17 and 5 HUMCAlXIAT19. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 1216 1308 HUMCAlXIA_T17 1216 1308 HUIMCAlXIA T19 1216 1308 10 Segment cluster HUMCA1XIA-node_19 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HJMCAlXIA_T16, HUMCAIXIA_T17 and HUMCAIXIAT19. Table 34 below describes the starting and ending position of this segment on each transcript. 15 Table 34 - Segment location on transcripts Transcript name Segment Segment starting position ending position HTMCAIXIAT16 1523 1563 HUMCAXIAT17 1523 1563 HUMCA1XIAT19 1523 1563 Segment cluster HUMCAIXIAnode_21 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): HUMCAIXIA_T16, HUMCAIXIA_T17 and WO 2005/072050 PCT/IB2005/000433 565 HUMCA1XJIA_19. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 1564 1626 HUMCA1XIA17 1564 1626 HIJMCA1XIAT19 1564 1626 5 Segment cluster HUMCA1XIAnode_23 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, HUMCA1XIA_17 and 1-HMCAlXIA-T19. Table 36 below describes the starting and ending position of this segment 10 on each transcript. Table 36 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAXNIA16 1627 1668 HUMCA1XIA17 1627 1668 HUMCAIXIA 119 1627 1668 Segment cluster HUMCAIXIAnode_25 according to the present invention is supported 15 by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUJMCA1XIAT16, HUMCAIXIA_17 and HUIMCAIXIA19. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 566 Transcript name Segment Segment starting position ending position HUMCA1XIAT16 1669 1731 HUMCA1XIA_T17 1669 1731 HIUMCAlXIAT19 1669 1731 Segment cluster HUMCAIXIA node-27 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAXIAT16, HUMCA1XIA_T17 and HUMCA 1 XIAT 19. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript nam Segment Segment starting position ending position HUMCA1XIAT16 1732 1806 HUMCA 1XIAT 17 1732 1806 HUMCAIXIAT 19 1732 1806 10 Segment cluster HJMCA1XIAnode_29 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCALXIAT16, HUMCAIXIA_T17 and HIUMCAXIAT19. Table 39 below describes the starting and ending position of this segment 15 on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting position ending position LIMCA1XIAT16 1807 1890 WO 2005/072050 PCT/IB2005/000433 567 HUMCAIXIAT17 1807 1890 HUMCA1XIAT19 1807 1890 Segment cluster HJMCAIXIA node_31 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA_T16, HUMCAlXIA_T17 and H-MCA1XIA_T19. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA T16 1891 1947 HUMCA1XIAT17 1891 1947 HUMCA1XIA_T19 1891 1947 10 Segment cluster HLMCAlXIAnode_33 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HIUMCAIXIA_T16, -HMCAIXIA_T17 and HUMCA1XIA_T19. Table 41 below describes the starting and ending position of this segment 15 on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T16 1948 2001 HUMCA1XIA_T17 1948 2001 HUMCA1XIAT19 1948 2001 WO 2005/072050 PCT/IB2005/000433 568 Segment cluster HJMCAIXIA_node_35 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAXIA-T16, H-UMCAXIAT17 and HUMCAIXIAT19. Table 42 below describes the starting and ending position of this segment 5 on each transcript. Table 42 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 2002 2055 HUMCA1XIA T17 2002 2055 HUJMCAIXIA_T19 2002 2055 Segment cluster HUJMCA1XIAnode_37 according to the present invention is supported 10 by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUIMCAlXIA_T16, HUMCAIXIA_T17 and HUMCA IXIA-T19. Table 43 below describes the starting and ending position of this segment on each transcript. Table 43 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T16 2056 2109 HUMCAXIAT17 2056 2109 HUMCA1XIA-T19 2056 2109 15 Segment cluster HLJMCAIXIA_node_39 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAXIAT16, HUMCA1XIA_T17 and WO 2005/072050 PCT/IB2005/000433 569 HJMCA1XIA_T19. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name Segment Segment starling position ending position HUMCAIXIAT16 2110 2163 HUMCA1XIAT17 2110 2163 HULfMCAlXIA_T19 2110 2163 5 Segment cluster HUMCAIXIAnode_41 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HTMCAIXIAT16, HUMCAlXIA_T17 and HUMCA1XIA-T19. Table 45 below describes the starting and ending position of this segment 10 on each transcript. Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HMTIVCAIXIAT16 2164 2217 HUMCAXIATI7 2164 2217 HUMCA1XIA_T19 2164 2217 Segment cluster HUMCAIXIA node_43 according to the present invention is supported 15 by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, HUMCA1XIA_T17 and HJMCAIXIA_T19. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 570 Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2218 2262 HUMCAlXIAT17 2218 2262 HUMCA1XIAT19 2218 2262 Segment cluster HUMCAIXIAnode-45 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIAT16 and HLTMCA1XIA_T17. Table 47 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts Transcript name Segment Segment starting position ending position HIJMCA1XIA_T16 2263 2316 TIUMCAIXIAT17 2263 2316 10 Segment cluster HUMCA1XIAnode_47 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT16, HUMCA1XIA_T17 and HTMCA1XIA_T19. Table 48 below describes the starting and ending position of this segment on each transcript. 15 Table 48 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUIVCA1XIA_T16 2317 2361 HUMCA1XIAT17 2317 2361 HUMCAlXIAT19 2263 2307 WO 2005/072050 PCT/IB2005/000433 571 Segment cluster HUMCAIXIAnode_49 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA_T16, HULMCA IXIAT17 and HUMCA IXIA-T19. Table 49 below describes the starting and ending position of this segment on each transcript. Table 49 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2362 2415 HUMCAIXIAT17 2362 2415 HUMCA1XIA_T19 2308 2361 10 Segment cluster HUMCAXIA_node_51 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16, HUMCAIXIA17 and HUMCAIXIAT19. Table 50 below describes the starting and ending position of this segment 15 on each transcript. Table 50 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 2416 2460 HUMCA1XIA_T17 2416 2460 IHUMCA1XIAT19 2362 2406 Segment cluster HUMCA1XIA node_57 according to the present invention is supported 20 by 4 libraries. The number of libraries was determined as previously described. This segment WO 2005/072050 PCT/IB2005/000433 572 can be found in the following transcript(s): HUMCAIXIA_T16. Table 51 below describes the starting and ending position of this segment on each transcript. Table 51 - Segment location on transcripts Transcript name Segment starting position ending position HUMCA1XIA T16 2461 2514 5 Segment cluster HIUMCAlXIA_node_59 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA_T16. Table 52 below describes the starting and ending position of this segment on each transcript. 10 Table 52 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2515 2559 Segment cluster HUMCAlXIAnode_62 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): HUMCAlXIA_T16. Table 53 below describes the starting and ending position of this segment on each transcript. Table 53 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT 16 2560 2613 WO 2005/072050 PCT/IB2005/000433 573 Segment cluster HUMCAIXIAnode_64 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HJMCAlXIA-T16. Table 54 below describes the starting and ending position of this segment on each transcript. 5 Table 54 - Segment location on transcripts Traoscript name Segment Segment starting position ending position HUMCA1XIAT16 2614 2658 Segment cluster HUMCAIXIAnode_66 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): HUMCAlXIAT16. Table 55 below describes the starting and ending position of this segment on each transcript. Table 55 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAXIAT16 2659 2712 15 Segment cluster HJMCAlXIAnode_68 according to the present invention is supported by 7 libraries. The number of libraries was determined as previoEly described. This segment can be found in the following transcript(s): HUMCAlXIA_T16. Table 56 below describes the starting and ending position of this segment on each transcript. Table 56 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIAT16 2713 2820 20 WO 2005/072050 PCT/IB2005/000433 574 Segment cluster HUMCAIXIAnode_70 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_Ti6. Table 57 below describes the 5 starting and ending position of this segment on each transcript. Table 57 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2821 2874 Segment cluster HUMCAlXIAnode_72 according to the present invention is supported 10 by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16. Table 58 below describes the starting and ending position of this segment on each transcript. Table 58 - Segment location on transcripts Transcript name Segment Segment starting position ending position HNIMCA1XIA_T16 2875 2928 15 Segment cluster HUMCAlXIA node_74 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT16. Table 59 below describes the starting and ending position of this segment on each transcript. 20 Table 59 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2929 2973 WO 2005/072050 PCT/IB2005/000433 575 Segment cluster HUMCA1XIAnode_76 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIAT16. Table 60 below describes the starting and ending position of this segment on each transcript. Table 60 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2974 3027 10 Segment cluster HUMCAIXIAnode_78 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA IXIA_T16. Table 61 below describes the starting and ending position of this segment on each transcript. Table 61 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 3028 3072 15 Segment cluster HUMCAlXIA_node_81 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16. Table 62 below describes the 20 starting and ending position of this segment on each transcript. Table 62 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072050 PCT/IB2005/000433 576 HUMCAlXIAT16 3073 3126 Segment cluster HUMCA1XIAnode_83 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HJMCAlXIA_T16. Table 63 below describes the starting and ending position of this segment on each transcript. Table 63 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIA_T16 3127 3180 10 Segment cluster HUMCA IXIA node_85 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA-T16. Table 64 below describes the starting and ending position of this segment on each transcript. Table 64 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 3181 3234 15 Segment cluster HfIUMCA IXIA node_87 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16. Table 65 below describes the 20 starting and ending position of this segment on each transcript. Table 65 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 577 Transcript name Segment Segment starting position ending position HUMCA1XIAT16 3235 3342 Segment cluster HUIMCA IXIA_node_89 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAIXIA_T16. Table 66 below describes the starting and ending position of this segment on each transcript. Table 66 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUJMCA1XIAT16 3343 3432 10 Segment cluster HUMCA1XIAnode_91 according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16. Table 67 below describes the starting and ending position of this segment on each transcript. Table 67 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T16 3433 3486 15 Transcript nucleic acid sequences: 20 Variant protein alignment to the previously known protein: WO 2005/072050 PCT/IB2005/000433 578 Sequence name: CA1BHUMAN_V5 Sequence documentation: 5 Alignment of: HUMCAlXIAP14 x CA1B_HUMANV5 Alignment segment 1/1: Quality: 10456.00 10 Escore: 0 Matching length: 1058 Total length: 1058 Matching Percent Similarity: 99.91 Matching Percent Identity: 99.91 15 Total Percent Similarity: 99.91 Total Percent Identity: 99.91 Gaps: 0 Alignment: 20 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 25 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 l i l l l l l l l l l l l l l l l l l l l i l l l l l l l l l l l l l l 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 3 0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 WO 2005/072050 PCT/IB2005/000433 579 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 5 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 10 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 1 5 | | | | | | | ||I | | | | | | | | | | | | | | | | | | | | | | | | | | | | |1 | | |1 | | | | 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 20 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 25 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 l i l l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l llIlI 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 30 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 I | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | WO 2005/072050 PCT/IB2005/000433 580 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 |||||||||||1 ||1 |||| ||| |||||lllil l11l1ll1lll ll l l1 l 11 l 5 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 10 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 15 701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750 701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750 751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800 20 751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800 801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850 25 801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850 851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900 851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900 30 901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950 WO 2005/072050 PCT/IB2005/000433 581 901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950 951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000 951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000 1001 AACKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050 10 1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050 1051 GPPGPVVS 1058 |H|M 1 1051 GPPGPVGS 1058 15 20 Sequence name: CA1BHUMAN Sequence documentation: 25 Alignment of: HUMCA1XIAP15 x CA1B_HUMAN Alignment segment 1/1: Quality: 7073.00 30 Escore: 0 WO 2005/072050 PCT/IB2005/000433 582 Matching length: 714 Total length: 714 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 10 - - 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 15 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 20 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 25 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 30 - - - 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 WO 2005/072050 PCT/IB2005/000433 583 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 5 | | | | | |I | | | | || | | | | | | | || | | | | | | | | | ||11 1 1 l1 l1 1 | | | || | | | | 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 10 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 15 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 20 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 25 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 30 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 WO 2005/072050 PCT/IB2005/000433 584 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 l l l l l l l 1 11|| | | | | | | | | | | | | | ||1l l l i I lii I | | | | | | 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 5 701 LPGPQGPIGPPGEK 714 701 LPGPQGPIGPPGEK 714 10 Sequence name: CA1BHUMAN 15 Sequence documentation: Alignment of: HUMCA1XIAP16 x CA1B_HUMAN 20 Alignment segment 1/1: Quality: 6795.00 Escore: 0 Matching length: 696 Total 25 length: 714 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 97.48 Total Percent Identity: 97.48 30 Gaps: 1 WO 2005/072050 PCT/IB2005/000433 585 Alignment: 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 5 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 10 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 15 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 25 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 30 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 WO 2005/072050 PCT/IB2005/000433 586 ||| ||1 | || |||| | | ||||| ||1111 1 1|| || |||| || | 1| |||1 ||1 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 5 | | |1 | | |11 |1| | | | | | | | | | | | | 1| | | | 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 10 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 15 551 AKGESGDPGPQGPRGVQGPPGPTGKPCKRGRPGADGGRGMPGEPGAKGDR 600 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 20 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA.. 648 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 649 ................ GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 682 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 683 LPGPQGPIGPPGEK 696 | | | | | | | ||I| | | 30 701 LPGPQGPIGPPGEK 714 WO 2005/072050 PCT/IB2005/000433 587 5 Sequence name: CAlBHUMAN Sequence documentation: 10 Alignment of: HUMCA1XIAP17 x CA1BHUMAN Alignment segment 1/1: Quality: 2561.00 15 Escore: 0 Matching length: 260 Total length: 260 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 20 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 25 . . - 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 30 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l WO 2005/072050 PCT/IB2005/000433 588 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 5 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 10 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 l i lli ll l i l l Il l ll i|| ||||| i l 1111 11il ||||||||||| 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 15 251 AQAQEPQIDE 260 I II 1 1 1I| 251 AQAQEPQIDE 260 20 DESCRIPTION FOR CLUSTER P20779 Cluster R20779 features 1 transcript(s) and 24 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 25 Table ] - Transcripts of interest Transcript Name Sequence ID No. R20779_T7 354 Table 2 - Segments of interest Segment Name Sequence ID No.

WO 2005/072050 PCT/IB2005/000433 589 R20779_node 0 355 R20779_node 2 356 R20779_node 7 357 R20779_node_9 358 R20779_node 18 359 R20779_node_21 360 R20779_node_24 361 R20779_node 27 362 R20779_node 28 363 R20779_node_30 364 R20779_node_31 365 R20779_node_32 366 R20779_node_1 367 R20779_node_3 368 R20779_node-10 369 R20779_node_11 370 R20779_node_14 371 R20779_node_17 372 R20779_node 19 373 R20779_node_20 374 R20779_node_22 375 R20779_node_23 376 R20779_node_25 377 R20779_node_29 378 Table 3 - Proteins of interest ProteinName Sequence ID No. Corresponding Transcript(s) 120779_P2 380 R20779_T7 WO 2005/072050 PCT/IB2005/000433 590 These sequences are variants of the known protein Stanniocalcin 2 precursor (SwissProt accession identifier STC2_HUJMAN; known also according to the synonyms STC-2; Stanniocalcin-related protein; STCRP; STC-related protein), SEQ ID NO: 379, referred to herein as the previously known protein. 5 Protein Stanniocalcin 2 precursor is known or believed to have the following function(s): Has an anti-hypocalcemic action on calcium and phosphate homeostasis. The sequence for protein Stanniocalcin 2 precursor is given at the end of the application, as "Stanniocalcin 2 precursor amino acid sequence". Protein Stanniocalcin 2 precursor localization is believed to be Secreted (Potential). 10 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cell surface receptor linked signal transduction; cell-cell signaling; nutritional response pathway, which are annotation(s) related to Biological Process; hormone, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component. 15 The GO assignment relies on information from one or more of the SwissProt/TremBI Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster R20779 can be used as a diagnostic marker according to overexpression of 20 transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previoLwly described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 33 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 25 Overall, the following results were obtained as shown with regard to the histograms in Figure 33 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors. 30 Table 4 - Normal tissue distribution WO 2005/072050 PCT/IB2005/000433 591 Name of Tissue Number Bone 825 Brain 0 Colon 0 epithelial 32 general 38 kidney 22 Liver 9 Lung 11 Lymph nodes 0 Breast 215 muscle 35 Ovary 36 pancreas 4 prostate so Skin 99 stomach 0 Uterus 4 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 Bone 5.9e-01 7.4e-01 1 0.2 1 0.1 Brain 2.5e-02 1.6e-02 2.2e-01 6.0 3.5e-02 8.0 Colon 1.7e-01 1.7e-01 1 1.3 7.7e-01 1.5 epithelial 1.7e-01 1.5e-03 5.9e-01 1.0 2.0e-04 2.0 general 2.4e-02 6.2e-07 7.6e-01 0.8 4.6e-05 1.6 kidney 4.3e-01 2.7e-01 6.2e-01 1.3 1.5e-01 2.0 Liver 8.3e-01 7.6e-01 1 0.8 3.3e-01 1.6 Lung 1.2e-01 1.4e-03 1.9e-01 2.9 1.6e-05 7.7 WO 2005/072050 PCT/IB2005/000433 592 Lymph nodes 3.le-01 1 1.0 1 1.4 Breast 6Se-01 6.8e-01 6.9e-01 0.8 3.6e-01 0.8 muscle 9.2e-01 4.8e-01 1 0.3 1.4e-03 1.4 Ovary 8.4e-01 7.le-01 9.0e-01 0.7 8.6e-01 0.8 pancreas 9.3e-01 6.8e-01 1 0.7 1.5e-01 2.0 prostate 9.le-01 5.0e-01 9.8e-01 0.4 5.7e-01 0.7 Skin 6.3e-01 7.5e-01 7.le-01 0.8 9.5e-01 0.3 stomach 1 4.5e-01 1 1.0 5.le-01 1.8 Uterus 7.le-01 2.6e-01 4.4e-01 1.7 4.le-01 1.8 For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously 5 described. The following oligonucleotides were found to hit this cluster but not other segments/transcripts below, shown in Table 6. Table 6 - Oligonucleotides related to this cluster Oligonucleotide name Overexpressed in cancers Chip reference R20779-0_0_30670 breast malignant tumors BRS As noted above, cluster R20779 features 1 transcript(s), which were listed in Table 1 10 above. These transcript(s) encode for protein(s) which are variant(s) of protein Stanniocalcin 2 precursor. A description of each variant protein according to the present invention is now provided. Variant protein R20779_P2 according to the present invention has an amino acid 15 sequence as given at the end of the application; it is encoded by transcript(s) R20779_T7. An alignment is given to the known protein (Stanniocalcin 2 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 593 Comparison report between R20779_P2 and STC2_HUMAN: 1.An isolated chimeric polypeptide encoding for R20779P2, comprising a first amino acid sequence being at least 90 % homologous to MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLV 5 NAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRH RFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids I - 169 of STC2_HUMAN, which also corresponds to amino acids 1 - 169 of R20779_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 10 95% homologous to a polypeptide having the sequence CYKIEITMPKRRKVKLRD corresponding to amino acids 170 - 187 of R20779P2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of R20779P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 15 at least about 90% and most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD in R20779_P2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein R20779_P2 also has the following non-silent SNPs (Single Nucleotide 25 Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R20779P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 594 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 16 L-> No 98 Q-> No 171 Y->C Yes 177 M->V Yes The glycosylation sites of variant protein R20779_P2, as compared to the known protein Stanniocalcin 2 precursor, are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation 5 site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 8 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 73 yes 73 Variant protein R20779_P2 is encoded by the following transcript(s): R20779_T7, for 10 which the sequence(s) is/are given at the end of the application. The coding portion of transcript R20779_T7 is shown in bold; this coding portion starts at position 1397 and ends at position 1957. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 15 R20779P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs SNP position on nucleotide Alterative nucleic acid Previously known SNP? sequence 1442 T-> No WO 2005/072050 PCT/IB2005/000433 595 1690 G-> No 1732 C -> T Yes 1867 G -> T Yes 1908 A->G Yes 1925 A -> G Yes 1968 G->A Yes 2087 C -> T No 2138 C -> T Yes 2270 C -> No 2443 A-> No 2478 G -> No 2479 C -> A No 2616 C -> A No 2941 C -> No 3196 ->A No 3479 T->G Yes 4290 C -> T Yes 4358 G->A Yes 5363 G->A No As noted above, cluster R20779 features 24 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster R20779_node_0 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 10 below describes the starting and 10 ending position of this segment on each transcript. Table 10 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 596 Transcript name Segment Segment starting position ending position R20779_T7 1 1298 Segment cluster R20779_node_2 according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): R20779_T7. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment Segment starting position ending position R0779_T7 1337 1506 10 Segment cluster R20779_node_7 according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 1548 1690 15 Segment cluster R20779_node_9 according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 13 below describes the starting and 20 ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 597 Table 13 - Segment location on transcripts Transcript name Segment Segment stitigPsiin ending position R20779_T7 1691 1838 Segment cluster R20779_node 18 according to the present invention is supported by 61 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2009 2176 10 Segment cluster R20779_node_21 according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 15 below describes the starting and ending position of this segment on each transcript. 15 Table 15 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2219 2796 Segment cluster R20779_node_24 according to the present invention is supported by 100 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072050 PCT/IB2005/000433 598 found in the following transcript(s): R20779_T7. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2977 3667 5 Segment cluster R20779_node_27 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 17 below describes the starting and ending position of this segment on each transcript. 10 Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 3673 3803 Segment cluster R20779_node_28 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): R20779_T7. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 3804 4050 WO 2005/072050 PCT/IB2005/000433 599 Segment cluster R20779_node_30 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779-T7. Table 19 below describes the starting and ending position of this segment on each transcript. 5 Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 4068 4193 Segment cluster R20779_node_31 according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be 10 found in the following transcript(s): R20779T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 4194 4424 15 Segment cluster R20779_node_32 according to the present invention is supported by 88 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 4425 5503 20 WO 2005/072050 PCT/IB2005/000433 600 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster R20779-node_1 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 1299 1336 10 Segment cluster R20779_node_3 according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 23 below describes the starting and 15 ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 1507 1547 Segment cluster R20779_node_10 according to the present invention can be found in the 20 following transcript(s): R20779_T7. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 601 Transcript name Segment Segment starting position ending position R20779_T7 1839 1849 Segment cluster R20779_node_11 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be 5 found in the following transcript(s): R20779_T7. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment Segment starting position ending position id0779_T7 1850 1902 10 Segment cluster R20779_node_14 according to the present invention is supported by I libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position I20779_T7 1903 1975 15 Segment cluster R20779_node_17 according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 27 below describes the starting and 20 ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 6 0 2 Table 27 - Segment location on transcripts Transcrip t name Segment Segment starting position ending position R20779_T7 1976 2008 Segment cluster R20779_node_19 according to the present invention can be found in the 5 following transcript(s): R20779_T7. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2177 2188 10 Segment cluster R20779_node_20 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2189 2218 15 Segment cluster R20779_node_22 according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 30 below describes the starting and 20 ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 603 Table 30 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779T7 2797 2899 Segment cluster R20779_node_23 according to the present invention is supported by 81 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 2900 2976 10 Segment cluster R20779_node_25 according to the present invention can be found in the following transcript(s): R20779_T7. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment Segment starting position ending position R20779_T7 3668 3672 15 Segment cluster R20779_node_29 according to the present invention can be found in the following transcript(s): R20779_T7. Table 33 below describes the starting and ending position of this segment on each transcript. 20 Table 33 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 604 Transcript name Segment Seg nt starting position ef&~position R20779_T7 4051 4067 Variant protein alignment to the previously known protein: 5 Sequence name: STC2_HUMAN Sequence documentation: Alignment of: R20779_P2 x STC2_HUMAN 10 Alignment segment 1/1: Quality: 1688.00 Escore: 0 15 Matching length: 171 Total length: 171 Matching Percent Similarity: 99.42 Matching Percent Identity: 99.42 Total Percent Similarity: 99.42 Total Percent 20 Identity: 99.42 Gaps: 0 Alignment: 25 1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50 1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50 WO 2005/072050 PCT/IB2005/000433 605 51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGK 100 111llll1llllll 11lll 1llll 11ll 1l1lll 111lllll illlllllll 51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGK 100 5 101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150 101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150 151 ENTRVIVEMIHFKDLLLHECY 171 10 1il l l l l l l l 151 ENTRVIVEMIHFKDLLLHEPY 171 DESCRIPTION FOR CLUSTER HSS 1OOPCB Cluster HSS100PCB features I transcript(s) and 3 segment(s) of interest, the names for 15 which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. HSS100PCB-Ti 381 Table 2 - Segments of interest Segment Name Sequence ID No. HSS100PCBnode_3 382 HSS100PCB-node_4 383 HSS100PCBnode_5 3S4 20 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) HSS100PCBP3 386 HSS100PCB_TI WO 2005/072050 PCT/IB2005/000433 606 These sequences are variants of the known protein S-1OOP protein (SwissProt accession identifier S0P_HUMAN), SEQ ID NO: 385, referred to herein as the previously known protein. 5 The sequence for protein S-100P protein is given at the end of the application, as "S -1 OOP protein amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 32 E->T 44 F->E The following GO Annotation(s) apply to the previously known protein. The following 10 annotation(s) were found: calcium binding; protein binding, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.chlsprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 15 Cluster HSS100PCB can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of suh transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 34 refer to weighted expression of ESTs in 20 each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 34 and Table 5. This cluster is overexpressed (at least at a minimum level) in the 25 following pathological conditions: a mixture of malignant tumors from different tissues.

WO 2005/072050 PCT/IB2005/000433 607 Table 5 - Normal tissue distribution Name of Tissue Number Bladder 41 Colon 37 Epithelial 38 General 22 Kidney 0 Liver 0 Lung 18 Breast 0 bone marrow 0 Ovary 0 pancreas 0 prostate 46 stomach 553 Uterus 13 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 bladder 3.3e-01 2.9e-01 2.9e-02 2.8 3.5e-02 2.8 Colon 3.0e-01 1.9e-01 5.2e-01 1.2 2.4e-01 1.7 epithelial 4.7e-02 1.6e-02 2.0e-01 1.2 6.le-02 1.3 general 1.le-03 6.8e-05 1.4e-02 1.5 4.9e-04 1.7 kidney 6.5e-01 7.2e-01 5.8e-01 1.7 7.0e-01 1.4 Liver 9.le-01 4.9e-01 1 1.0 7.7e-02 2.1 Lung 6.8e-01 7.3e-01 2.2e-02 2.9 1.3e-01 1.7 Breast 2.8e-01 3.2e-01 4.7e-01 2.0 6.8e-01 1.5 bone marrow I 6.7e-01 1 1.0 2.8e-01 2.8 Ovary 2.6e-01 3.0e-01 4.7e-01 2.0 5.9e-01 1.7 WO 2005/072050 PCT/IB2005/000433 608 pancreas 3.3e-01 4.4e-01 7.6e-02 3.7 1.5e-01 2.8 prostate 9.le-01 9.3e-01 5.8e-01 0.6 7.6e-01 0.5 stomach 3.7e-01 3.2e-01 1 0.1 1 0.3 Uterus 9.4e-01 7.0e-01 1 0.6 4.le-01 1.1 As noted above, cluster HSS100PCB features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein S-1OOP protein. A description of each variant protein according to the present invention is now provided. 5 Variant protein HSSIOOPCB_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSS 1 OOPCB_TI. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 10 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSS100PCB_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the 15 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCBP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence I M ->R Yes 11 M ->L Yes 20 L -> F Yes 20 WO 2005/072050 PCT/IB2005/000433 609 Variant protein HSSIOOPCBP3 is encoded by the following transcript(s): HSS 1 OOPCB_TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSIOOPCB_Ti is shown in bold; this coding portion starts at position 1057 and ends at position 1533. The transcript also has the following SNPs as listed in 5 Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCBP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 52 C ->T Yes 107 A ->C Yes 458 C ->T Yes 468 A ->G Yes 648 C -> T Yes 846 C ->G Yes 882 G->A Yes 960 C -> T No 965 C->T Yes 1058 T -> G Yes 1087 A ->C Yes 1114 C ->T Yes 1968 G ->A Yes 1971 C ->T Yes 2010 C ->A Yes 2099 G No 10 As noted above, cluster HSS100PCB features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are WO 2005/072050 PCT/IB2005/000433 610 of particular interest. A description of each segment according to the present invention is now provided. Segment cluster HSS 100PCBnode_3 according to the present invention is supported by 5 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_TI. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSS100PCBTi 1 1133 10 Segment cluster HSS 1 OOPCBnode_4 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1. Table 10 below describes the starting and ending position of this segment on each transcript. 15 Table 10 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSS100PCB_Ti 1134 1923 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides 20 were found to hit this segment (in relation to breast cancer), shown in Table 11. Table 11 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference HSSI0OPCB 0_0_12280 breast malignant tumors BRS WO 2005/072050 PCT/IB2005/000433 611 Segment cluster HSS100PCB-node_5 according to the present invention is supported by 141 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB-Ti. Table 12 below describes the starting 5 and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment Segment starting'positilon ending position HSS100PCB_Ti 1924 2201 10 WO 2005/072050 PCT/IB2005/000433 612 DESCRIPTION FOR CLUSTER HSCOC4 Cluster HSCOC4 features 19 transcript(s) and 79 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 5 Table 1 - Transcripts of interest Transcript Name Sequence ID No. HSCOC4_PEA 1 Ti 387 HSCOC4_PEA_1 T2 388 HSCOC4_PEAI__T3 389 HSCOC4_PEA_1_T4 390 HSCOC4_PEA_1_T5 391 HSCOC4-PEA__T7 392 HSCOC4_PEA_1_T8 393 HSCOC4_PEA_1_T11 394 HSCOC4-PEA-1_T12 395 HSCOC4_PEA_1_T14 396 HSCOC4-PEA_1-Ti5 397 HSCOC4_PEAlT20 398 HSCOC4_PEA_1_T21 399 HSCOC4_PEA_1_T25 400 HSCOC4_PEA_1_T28 401 HSCOC4_PEA_1_T30 402 HSCOC4_PEA_1_T31 403 HSCOC4-PEA_1_T32 404 HSCOC4_PEA_1_T40 405 Table 2 - Segments of interest Segment Name Sequence ID No. HSCOC4_PEA_-node_1 406 WO 2005/072050 PCT/IB2005/000433 613 HSCOC4-PEAI node-5 407 HSCOC4_PEA_1 node_7 408 HSCOC4_PEA_1_node_30 409 HSCOC4_PEA_1_node_33 410 HSCOC4_PEA_1_node_35 411 HSCOC4_PEA 1node_37 412 HSCOC4_PEA_1_node_39 413 HSCOC4_PEA_1_node_43 414 HSCOC4_PEA_1_node_48 415 HSCOC4_PEA-1 node_49 416 HSCOC4_PEA_1 node-51 417 HSCOC4_PEA_1_node_58 418 HSCOC4-PEA_1_node_59 419 HSCOC4_PEA_1node_62 420 HSCOC4_PEA_1_node_66 421 HSCOC4_PEA_1_node_72 422 HSCOC4_PEA_1_node_77 423 HSCOC4_PEA_1_node_79 424 HSCOC4_PEA_1_node_93 425 HSCOC4_PEA_1-node 100 426 HSCOC4_PEA_1_node 105 427 HSCOC4_PEA1 node_107 428 HSCOC4-PEA_1_node_108 429 HSCOC4_PEA_1_node-109 430 HSCOC4_PEA_1_node 110 431 HSCOC4_PEA_ node 112 432 HSCOC4_PEA_1 node 113 433 HSCOC4_PEA_1_node_2 434 HSCOC4_PEA_1_node_8 435 HSCOC4_PEA_1 node_10 436 WO 2005/072050 PCT/IB2005/000433 614 HSCOC4_PEA_1_node_12 437 HSCOC4_PEA_1_node_14 438 HSCOC4_PEA_1_node_17 439 HSCOC4-PEA 1 node_19 440 HSCOC4_PEA_1-node_21 441 HSCOC4_PEA-1_node_22 442 HSCOC4_PEA_1_node_28 443 HSCOC4_PEA-_1node_29 444 HSCOC4_PEA_1_node_41 445 HSCOC4_PEA1_-node-45 446 HSCOC4_PEA_1_node_47 447 HSCOC4_PEA_1_node_50 448 HSCOC4_PEA-1_node_53 449 HSCOC4_PEA1_-node_55 450 HSCOC4-PEA_-node 57 451 HSCOC4_PEA_1_node_60 452 HSCOC4_PEA-_1node_64 453 HSCOC4_PEA_1 node_69 454 HSCOC4-PEA-1node_70 455 HSCOC4_PEA_1_node_71 456 HSCOC4-PEA_1_node_73 457 HSCOC4_PEA_1_node_74 458 HSCOC4_PEA_1_node_75 459 HSCOC4_PEA_1_node_76 460 HSCOC4_PEA_1_node_78 461 HSCOC4_PEA-1_node_80 462 HSCOC4_PEA-_1node_82 463 HSCOC4_PEA_1_node_83 464 HSCOC4_PEA_1_node_84 465 HSCOC4_PEA_1_node_85 466 WO 2005/072050 PCT/IB2005/000433 615 HSCOC4_PEA I node 86 467 HSCOC4_PEA_1_node_87 468 HSCOC4_PEA_1 node 88 469 HSCOC4_PEA_1 node_89 470 HSCOC4_PEA_1 node 90 471 HSCOC4_PEA 1 node 91 472 HSCOC4_PEAInode_92 473 HSCOC4_PEA_1_node_94 474 HSCOC4_PEA_-node_96 475 HSCOC4_PEA_1_node_97 476 HSCOC4_PEA_1_node_98 477 HSCOC4_PEA_1_node_99 478 HSCOC4-PEA_1_node_101 479 HSCOC4_PEA- _node-102 480 HSCOC4_PEA-1 node_103 481 HSCOC4-PEA_1_node 104 482 HSCOC4_PEA_1 node 106 483 HSCOC4_PEA_1 node 111 484 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) HSCOC4_PEA 1_P3 488 HSCOC4_PEA-I_Ti HSCOC4_PEA_1_P5 489 HSCOC4_PEA_1_T3 HSCOC4_PEA_1_P6 490 HSCOC4_PEA_1_T4 HSCOC4_PEA_1_P12 491 HSCOC4_PEA_1_T1l HSCOC4_PEA_1_P15 492 HSCOC4_PEA_1_T14 HSCOC4_PEA_-P16 493 HSCOC4_PEA_1_TI5 HSCOC4_PEA_1_P20 494 HSCOC4_PEA_1_T20 HSCOC4_PEA-_P9 495 HSCOC4_PEA-_IT21 WO 2005/072050 PCT/IB2005/000433 616 HSCOC4_PEA1 _P22 496 HSCOC4_PEA_1_T25 HSCOC4_PEA_1 P23 497 HSCOC4_PEAIT28 HSCOC4_PEA_1_P24 498 HSCOC4_PEA_1_T30 HSCOC4_PEA 1 P25 499 HSCOC4_PEA_1_T31 HSCOC4_PEA 1 P26 500 HSCOC4_PEA_1_T32 HSCOC4-PEA_1_P30 501 HSCOC4_PEAI_T40 HSCOC4_PEA-lP38 502 HSCOC4_PEA-lT2 HSCOC4_PEA 1_P39 503 HSCOC4_PEA_1_T5 HSCOC4_PEA 1_P40 504 HSCOC4_PEA_1_T7 HSCOC4_PEAlP41 505 HSCOC4_PEA-lT8 HSCOC4_PEA_1_P42 506 HSCOC4_PEA_1_T12 These sequences are variants of the known protein Complement C4 precursor [Contains: C4a anaphylatoxin] (SwissProt accession identifier C04_HIMAN) SEQ ID NO: 485), referred to herein as the previously known protein. 5 Protein Complement C4 precursor [Contains: C4a anaphylatoxin] is known or believed to have the following function(s): C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated CI which removes from the alpha chain the C4a anaphylatoxin. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth 10 muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. The sequence for protein Complement C4 precursor [Contains: C4a anaphylatoxin] is given at the end of the application, as "Complement C4 precursor [Contains: C4a anaphylatoxin] amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. 15 Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 477 R-> W (in allotype C4A6). /FTId=VAR_001987.

WO 2005/072050 PCT/IB2005/000433 617 726 P -> L (in allotype C4A3). /FTId=VAR_001988. 1073 D -> G (in allotype C4A1, allotype C4B1 and allotype C4B3). /FTId=VAR_001989. 1120 - 1125 PCPVLD -> LSPVIH (in allotype C4B). /FTId=VAR_001990. 1176 N -> S (in allotype C4A1, allotype C4BI, allotype C4B3 and allotype C4B5). /FTId=VAR_001991. 1201 S -> T (in allotype C4A6, allotype C4A3, allotype C4A1 and allotype C4B). /FTId=VAR_001992. 1207 V -> A (in allotype C4A1, allotype C4B1, allotype C4B2 and allotype C4B3). /FTId=VAR_001993. 1210 L -> R (in allotype C4A I, allotype C4BI, allotype C4B2 and allotype C4B3). /FTId=VAR_001994. 1286 S -> A (in allotype C4A6, allotype C4A1, allotype C4A3A and allotype C4B). /FTId=VAR_001995. 1- 12 MRLLWGLIWASS -> PREVRSVCLSAT 347 S -> Y 418 V->A 727 D->N 907 A->T 980-981 VT -> LQ 1013 Q ->E 1317 I->F 1418- 1420 Missing 1654 T->RA 1698 H -> Q The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: muscle contraction regulation; inflammatory response; complement activation; complement activation, classical pathway, which are annotation(s) related to Biological Process; complement component; proteinase inhibitor, which are annotation(s) WO 2005/072050 PCT/IB2005/000433 618 related to Molecular Function; and extracellular; extracellular space, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available 5 from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HSCOC4 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of 10 the table and the numbers on the y-axis of Figure 35 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 15 Figure 35 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer. Table 5 - Normal tissue distribution Name of Tissue Number adrenal 853 bladder 328 bone 6 brain ill colon 245 epithelial 264 general 163 head and neck 0 kidney 141 liver 4109 WO 2005/072050 PCT/IB2005/000433 619 lung 64 lymph nodes 120 breast 96 bone marrow 0 ovary 116 pancreas 20 prostate 4 stomach 36 T cells 0 Thyroid 12 uterus 127 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 adrenal 5.6e-0l 5.9e-01 2.5e-06 0.3 4.3e-04 0.3 bladder 5.0e-01 6.6e-01 6.3e-01 0.9 9.le-01 0.6 bone 5.5e-01 5.8e-0l 1 1.1 7.0e-01 1.3 brain 4.6e-03 6.2e-02 7.7e-11 3.0 3.2e-05 1.7 colon 8.Oe-01 8.3e-01 9.8e-01 0.4 9.9e-01 0.4 epithelial 1.7e-01 9.2e-01 9.3e-07 1.3 9.7e-01 0.7 general 3.2e-04 6.le-01 1.5e-31 2.1 1.9e-03 1.1 head and neck 1.2e-01 2.le-01 1 1.2 1 1.1 kidney 6.9e-01 S.le-01 1.2e-04 2.4 1.5e-02 1.5 liver 7.le-01 7.2e-01 5.0e-04 0.2 1 0.1 lung 2.9e-01 7.le-01 4.2e-02 1.7 5.le-01 0.8 lymph nodes 6.3e-01 8.2e-01 9.0e-01 0.5 1 0.3 breast 4.0e-02 1.8e-01 2.le-06 6.0 3.9e-03 3.0 bone marrow 1 6.7e-0I 1 1.0 2.8e-01 2.8 ovary 6.6e-01 7.3e-01 1.3e-01 1.5 3.6e-01 1.1 WO 2005/072050 PCT/IB2005/000433 620 pancreas 1.7e-02 9.9e-02 4.8e-10 7.6 2.9e-07 5.1 prostate 5.8e-01 6.3e-01 4.le-02 3.9 1.8e-03 3.8 stomach 2.7e-01 7.5e-01 1.le-01 1.5 6.5e-01 0.8 T cells 1 6.7e-01 1 1.0 7.2e-01 1.4 Thyroid 3.4e-01 3.4e-01 3.0e-01 2.2 3.0e-01 2.2 uterus 1.2e-01 5.3e-01 6.6e-02 1.4 5.4e-01 0.8 As noted above, cluster HSCOC4 features 19 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Complement C4 precursor [Contains: C4a anaphylatoxin]. A description of each variant protein according to the present invention is now provided. 5 Variant protein HSCOC4_PEA_1_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA-1_Ti. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or 10 more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4_PEA_1_P3 and C04_HUMAN: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P3, comprising a first 15 amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGiLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 20 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTELVNGQSHSLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVTREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA 25 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS WO 2005/072050 PCT/IB2005/000433 621 LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 5 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTV corresponding to amino acids 1 865 of C04__HUMAN, which also corresponds to amino acids 1 - 865 of HSCOC4_PEA_1_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RPHRSLSIQELGEPGPSEGWGG corresponding to amino 10 acids 866 - 887 of HSCOC4_PEAlP3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence RPHRSLSIQELGEPGPSEGWGG in HSCOC4_PEA_1_P3. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 20 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the 25 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 622 SNP position(s) on amino Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L->V Yes 183 G -> No 211 G -> No 322 A -> No 322 A -> V No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K -> E Yes 726 P->L Yes 869 R->G Yes The glycosylation sites of variant protein HSCOC4_PEAl_P3, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the glycosylation site is present in the variant protein; and the last colurnm indicates whether the position is different on the variant protein). Table 8 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 yes 862 226 yes 226 1328 no WO 2005/072050 PCT/IB2005/000433 623 The phosphorylation sites of variant protein HSCOC4_PEA_1_P3, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 9 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the phosphorylation site is present in the variant protein; and the last colunm indicates whether the position is different on the variant protein). Table 9 - Phosphotylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1420 no 1422 no 1417 no Variant protein HSCOC4-PEA_1_P3 is encoded by the following transcript(s): 10 HSCOC4_PEA_1-TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T1 is shown in bold; this coding portion starts at position 501 and ends at position 3161. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein HSCOC4_PEA-lP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A -> G Yes 884 G -> No 921 C -> G Yes 1049 C-> No 1131 G-> No WO 2005/072050 PCT/IB2005/000433 624 1465 C-> No 1465 C -> T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G->A Yes 2540 C->T No 2677 C -> T Yes 2975 C ->T Yes 3105 A-> G Yes 3167 G -> A Yes 3228 T-> C Yes 3259 G->T Yes 3332 G->A Yes 3490 A->C Yes 3569 T-> C Yes 3724 G->T Yes 3831 A-> G Yes 3898 C -> A Yes 3972 C -> T Yes 3975 G-> C Yes 3983 T-> A Yes 3986 G-> C Yes WO 2005/072050 PCT/IB2005/000433 625 3988 C->T Yes 4140 G ->A Yes 4147 T C Yes 4228 C ->G Yes 4233 C ->T Yes 4242 G -> T Yes 4243 G -> C Yes 4339 G ->A Yes 4345 C -> G Yes 4348 G->A Yes 4469 G -> T Yes 4562 A->T Yes 4781 A->G No 4873 T->C Yes 5007 G -> No 5423 C -> G Yes 5634 G->C No 5677 G -> A Yes 5687 A-> C Yes 5862 A->C Yes 5868 G->A Yes 5933 A -> C Yes Variant protein HSCOC4_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T3. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief WO 2005/072050 PCT/IB2005/000433 626 description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4_PEA _P5 and CO4_HUMAN: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEAlP5, comprising a first 5 amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 10 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHIYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA 15 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding 20 to amino acids 1 - 818 of C04_-HUMAN, which also corresponds to amino acids 1 - 818 of HSCOC4_PEA_1_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least*95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS corresponding to amino acids 819 - 843 of HSCOC4_PEA-lP5, wherein said first amino acid 25 sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEALP5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS in HSCOC4_PEA_1_P5. 30 WO 2005/072050 PCT/IB2005/000433 627 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAl_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 1] - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L ->V Yes 183 G-> No 211 G-> No 322 A-> No 322 A->V No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H ->P Yes 608 L->V Yes 617 K -> E Yes 726 P -> L Yes 829 L->P Yes WO 2005/072050 PCT/IB2005/000433 628 830 L->I Yes 840 S->P Yes The glycosylation sites of variant protein HSCOC4_PEA_1_P5, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 12 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 no 226 yes 226 1328 no The phosphorylation sites of variant protein HSCOC4_PEAlP5, as compared to the 10 known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 13 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 13 - Phosphorylation sites) Position(s) on known amino Present in variant protein? acid sequence 1420 no 1422 no 1417 no 15 WO 2005/072050 PCT/IB2005/000433 629 Variant protein HSCOC4-PEAl-P5 is encoded by the following transcript(s): HSCOC4_PEAl-T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1-T3 is shown in bold; this coding portion starts at position 501 and ends at position 3029. The transcript also has the following SNPs as listed in 5 Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAl-P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C->T Yes 1985 C -> T Yes 2146 A -> C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A ->G Yes 2435 G ->A Yes WO 2005/072050 PCT/IB2005/000433 630 2540 C ->T No 2677 C ->T Yes 2986 T ->C Yes 2988 C -> A Yes 3018 T-> C Yes 3070 C -> T Yes 3081 C -> A Yes 3093 A ->G Yes 3101 G ->A Yes 3106 G ->A Yes 3174 G ->A Yes 3193 A ->G Yes 3201 T->C Yes 3233 C -> T Yes 3363 A -> G Yes 3425 G -> A Yes 3486 T->C Yes 3517 G->T Yes 3590 G->A Yes 3748 A -> C Yes 3827 T->C Yes 3982 G->T Yes 4089 A-> G Yes 4156 C -> A Yes 4230 C -> T Yes 4233 G-> C Yes 4241 T->A Yes 4244 G -> C Yes 4246 C -> T Yes 4398 G->A Yes WO 2005/072050 PCT/IB2005/000433 631 4405 T->C Yes 4486 C -> G Yes 4491 C ->T Yes 4500 G -> T Yes 4501 G-> C Yes 4597 G -> A Yes 4603 C -> G Yes 4606 G->A Yes 4727 G->T Yes 4820 A->T Yes 5039 A->G No 5131 T->C Yes 5265 G -> No 5681 C->G Yes 5892 G->C No 5935 G -> A Yes 5945 A -> C Yes 6120 A -> C Yes 6126 G -> A Yes 6191 A -> C Yes Variant protein HSCOC4_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEAIT4. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P6 and C04_HUMAN: WO 2005/072050 PCT/IB2005/000433 632 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_lP6, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 5 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHILDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 10 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKV/FEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTA-KRCCQDGVTR 15 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSV}HVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL 20 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKG corresponding to amino acids 1 - 1052 of C04_HUMAN, which also corresponds to amino acids 1 - 1052 of HSCOC4-PEA-1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP corresponding to amino acids 1053 1084 of HSCOC4_PEA_lP6, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEAlP6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP in HSCOC4_PEA_1_P6.

WO 2005/072050 PCT/IB2005/000433 633 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence, 128 Q-> No 141 L-> V Yes 183 G -> No 211 G -> No 322 A -> No 322 A->V No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes WO 2005/072050 PCT/IB2005/000433 634 872 V->A Yes 907 A->T Yes 959 E->D Yes 1062 G->V Yes 1068 T-> Yes The glycosylation sites of variant protein HSCOC4_PEA_1_P6, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 16 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 16 - Glycosvlation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 yes 862 226 yes 226 1328 no The phosphorylation sites of variant protein HSCOC4_PEA_lP6, as compared to the 10 known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 17 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 17 - Phosphoiylation site(s) Position(s) on known amino Present in variant protein? acid sequence 1420 no 1422 no WO 2005/072050 PCT/IB2005/000433 635 1417 no Variant protein HSCOC4_PEA-lP6 is encoded by the following transcript(s): HSCOC4_PEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T4 is shown in bold; this coding portion starts at 5 position 501 and ends at position 3752. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAl-P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 18 - Nucleic acid SNPs SNP position on ncleotide Alternative nucleic acid Preyiously known SNP? sequence 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C -> A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G-> A Yes 2322 C -> G Yes WO 2005/072050 PCT/IB2005/000433 636 2349 A -> G Yes 2435 G-> A Yes 2540 C ->T No 2677 C -> T Yes 2975 C -> T Yes 3115 T-> C Yes 3146 G-> T Yes 3219 G->A Yes 3377 A -> C Yes 3456 T->C Yes 3611 G->T Yes 3685 G->T Yes 3702 A-> Yes 3897 A -> G Yes 3964 C -> A Yes 4038 C->T Yes 4041 G -> C Yes 4049 T->A Yes 4052 -G -> C Yes 4054 C->T Yes 4206 G->A Yes 4213 T-> C Yes 4294 C -> G Yes 4299 C -> T Yes 4308 G -> T Yes 4309 G-> C Yes 4405 G -> A Yes 4411 C -> G Yes 4414 G->A Yes 4535 G -> T Yes WO 2005/072050 PCT/IB2005/000433 637 4628 A->T Yes 4847 A -> G No 4939 T->C Yes 5073 G-> No 5489 C -> G Yes 5700 G -> C No 5743 G -> A Yes 5753 A -> C Yes 5928 A -> C Yes 5934 G -> A Yes 5999 A -> C Yes Variant protein HSCOC4_PEA_1_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA-1_T11. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4-PEA_1_P12 and C04_HUMAN_Vi (SEQ ID NO: 486): 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1-P12, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR 15 NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR

GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE

WO 2005/072050 PCT/IB2005/000433 638 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDIPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS 5 LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAES LRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 10 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS 15 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDP MPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKV corresponding to amino acids 1 - 1380 of C04_-HUMANV1, which also corresponds to amino acids 1 - 1380 of HSCOC4_PEA-l_P12, 20 and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RAREGVGPGTGGGEGVE corresponding to amino acids 1381 - 1397 of HSCOC4_PEA_1_P12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a tail of HSCOC4-PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RAREGVGPGTGGGEGVE in HSCOC4_PEA_1_P12. 30 It should be noted that the known protein sequence (C04_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino WO 2005/072050 PCT/IB2005/000433 639 acid sequence for C04_HUMANV 1. These changes were previously known to occur and are listed in the table below. Table 19 - Changes to C04_-HUMAN_VI SNP positions) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA-1_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 20 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q -> No 141 L -> V Yes WO 2005/072050 PCT/IB2005/000433 640 183 G-> No 211 G-> No 322 A-> No 322 A->V No 347 S->Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V->A Yes 907 A->T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D -> H Yes 1176 S -> N Yes 1207 A->V Yes 1210 R->L Yes 1286 A-> S Yes 1317 I->F Yes Variant protein HSCOC4_PEA_1_P12 is encoded by the following transcript(s): HSCOC4_PEA_1T1 1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T 11 is shown in bold; this coding portion starts 5 at position 501 and ends at position 4691. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative WO 2005/072050 PCT/IB2005/000433 641 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA._I-P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 21 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence: 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G ->A Yes 2540 C ->T No 2677 C -> T Yes 2975 C -> T Yes 3115 T -> C Yes 3146 G -> T Yes WO 2005/072050 PCT/IB2005/000433 642 3219 G-> A Yes 3377 A-> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C -> T Yes 3862 G-> C Yes 3870 T-> A Yes 3873 G-> C Yes 3875 C -> T Yes 4027 G-> A Yes 4034 T-> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G -> T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G -> A Yes 4356 G-> T Yes 4449 A-> T Yes 4859 C -> T Yes 4876 C -> A Yes 4882 C -> G Yes 4924 G -> A Yes 5205 C -> G Yes 5596 C -> T Yes 5717 A-> G No 5809 T-> C Yes WO 2005/072050 PCT/IB2005/000433 643 -5943 No 6359 C -> G Yes 6570 G -> C No 6613 G->A Yes 6623 A -> C Yes 6798 A -> C Yes 6804 G -> A Yes 6869 A -> C Yes Variant protein HSCOC4_PEA-I_P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T14. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P15 and C04_HUMAN_VI: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P15, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSV[DGAKQYRNGESVKLHLETDS

LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG

WO 2005/072050 PCT/IB2005/000433 644 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVI T LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 5 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALIIHGLAVFQDEGAEPLKQRVEASISKASS 10 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQ corresponding to amino acids 1 - 1359 of C04_HUMAN_VI, which also corresponds to amino.acids 1 - 1359 of HSCOC4_PEA_1_P15, and a second amino acid 15 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL corresponding to amino acids 1360 - 1415 of HSCOC4-PEA_1_P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL in 25 HSCOC4_PEA_1_P15. It should be noted that the known protein sequence (C04_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04_-TUMAN_Vi. These changes were previously known to occur and are 30 listed in the table below.

WO 2005/072050 PCT/IB2005/000433 645 Table 22 - Changes to C04_HUMA N_Vi SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HSCOC4_PEA-1_P15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P15 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 23 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L -> V Yes 183 G -> No 211 G -> No WO 2005/072050 PCT/IB2005/000433 646 322 A-> V No 322 A-> No 347 S ->Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K ->E Yes 726 P -> L Yes 872 V-> A Yes 907 A -> T Yes 959 E-> D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S -> N Yes 1207 A->V Yes 1210 R->L Yes 1286 A->S Yes 1317 I->F Yes 1387 Q -> H Yes 1411 R->C Yes Variant protein HSCOC4_PEA_1_P15 is encoded by the following transcript(s): HSCOC4_PEA_1_T14, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T14 is shown in bold; this coding portion starts 5 at position 501 and ends at position 4745. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative WO 2005/072050 PCT/IB2005/000433 647 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA._lP15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 24 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A-> G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C -> No 1465 C -> T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C -> T Yes 2146 A->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G ->A Yes 2540 C->T No 2677 C ->T Yes 2975 C -> T Yes 3115 T-> C Yes 3146 G -> T Yes WO 2005/072050 PCT/IB2005/000433 648 3219 G ->A Yes 3377 A-> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C-> T Yes 3862 G -> C Yes 3870 T-> A Yes 3873 G-> C Yes 3875 C ->T Yes 4027 G -> A Yes 4034 T-> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G -> A Yes 4356 G-> T Yes 4449 A-> T Yes 4661 A-> C Yes 4731 C -> T Yes 4872 A-> G Yes 4905 C -> T Yes 5061 A-> G No 5153 T-> C Yes 5287 G -> No 5703 C -> G Yes WO 2005/072050 PCT/IB2005/000433 649 5914 G-> C No 5957 G->A Yes 5967 A -> C Yes 6142 A->C Yes 6148 G ->A Yes 6213 A-> C Yes Variant protein HSCOC4_PEA_1_P16 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA-1-TI5. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4-PEA_1_P16 and C04_HUMAN_V1: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA__1P16, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKR-LVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 25 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID WO 2005/072050 PCT/IB2005/000433 650 EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL 5 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR 10 QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPK corresponding to amino acids 1 - 1457 of C04-HUMAN_V I, which also corresponds to amino acids 1 - 1457 of HSCOC4_PEA_1_P16, and a second amino acid sequence being at least 70%, optionally at 15 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AERQGGAVWHGHRGRHPPEWIPRPAC corresponding to amino acids 1458 - 1483 of HSCOC4-PEA-_P16, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AERQGGAVWHGHRGRHPPEWIPRPAC in HSCOC4_PEA_1_P16. 25 It should be noted that the known protein sequence (CO4_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04_HUMAN_VI. These changes were previously known to occur and are listed in the table below. Table 25 - Changes to C04_HUMAN_VI WO 2005/072050 PCT/IB2005/000433 651 SNP positions) on fype of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 5 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure. Variant protein HSCOC4_PEA-1_P16 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 26, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 26 - Anino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L-> V Yes 183 G-> No 211 G-> No 322 A-> No 322 A -> V No WO 2005/072050 PCT/IB2005/000433 652 347 S ->Y Yes 423 Q -No 478 P->L Yes 549 H ->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V->A Yes 907 A->T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S ->N Yes 1207 A-> V Yes 1210 R->L Yes 1286 A -> S Yes 1317 I->F Yes 1390 K->E No Variant protein HSCOC4_PEA_1_P16 is encoded by the following transcript(s): HSCOC4_PEA_1T15, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4-PEA_1_T15 is shown in bold; this coding portion starts 5 at position 501 and ends at position 4949. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4-PEA_-P16 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072050 PCT/IB2005/000433 653 Table 27 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C-> A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G -> A Yes 2540 C -> T No 2677 C -> T Yes 2975 C -> T Yes 3115 T-> C Yes 3146 G->T Yes 3219 G->A Yes 3377 A -> C Yes 3456 T-> C Yes WO 2005/072050 PCT/IB2005/000433 654 3611 G->T Yes 3718 A->G Yes 3785 C->A Yes 3859 C ->T Yes 3862 G-> C Yes 3870 T->A Yes 3873 G-> C Yes 3875 C ->T Yes 4027 G->A Yes 4034 T-> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G->A Yes 4356 G->T Yes 4449 A -> T Yes 4668 A -> G No 4760 T->C Yes 5263 C -> G Yes 5474 G-> C No 5517 G->A Yes 5527 A-> C Yes 5702 A-> C Yes 5708 G -> A Yes 5773 A -> C Yes WO 2005/072050 PCT/IB2005/000433 655 Variant protein HSCOC4-PEA_1_P20 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA_1_T20. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or 5 more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4_PEA_1_P20 and CO4_HUMAN.V1: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEAL-P20, comprising a 10 first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWISARFSDGLESNSSTQFEVKKYVL 15 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDH HLA 20 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 25 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ 30 DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS

FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV

WO 2005/072050 PCT/IB2005/000433 656 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQ corresponding to amino acids 1 - 1303 of C04_HUMAN_VI, which also corresponds to amino acids 1 - 1303 of HSCOC4_PEA_lP20, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 5 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH corresponding to amino acids 1304 - 1349 of HSCOC4_PEA_1_P20, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEAl-P20, comprising a 10 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH in HSCOC4_PEA_1_P20. 15 It should be noted that the known protein sequence (C04_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04-HUMAN-V1. These changes were previously known to occur and are listed in the table below. Table 28 - Changes to C04_HUMAN_Vi SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized WO 2005/072050 PCT/IB2005/000433 657 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. 5 Variant protein HSCOC4_PEAlP20 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 29, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P20 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 29 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 128 Q -> No 141 L -> V Yes 183 G-> No 211 G-> No 322 A-> No 322 A->V No 347 S _> Y Yes 423 Q_> No 478 P->L Yes 549 H ->P Yes 608 L->V Yes 617 K -> E Yes 726 P -> L Yes 872 V -> A Yes 907 A -> T Yes 959 E -> D Yes WO 2005/072050 PCT/IB2005/000433 658 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S -> N Yes 1207 A->V Yes 1210 R->L Yes 1286 A -> S Yes 1312 R->G Yes 1344 D->V Yes Variant protein HSCOC4_PEA_1_P20 is encoded by the following transcript(s): HSCOC4_PEA-lT20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4-PEA_1_T20 is shown in bold; this coding portion starts 5 at position 501 and ends at position 4547. The transcript also has the following SNPs as listed in Table 30 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP20 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 30 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A -> G Yes 884 G No 921 C -> G Yes 1049 C-> No 1131 G -> No 1465 C -> No WO 2005/072050 PCT/IB2005/000433 659 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C -> T Yes 1985 C -> T Yes 2146 A-> C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A-> G Yes 2435 G->A Yes 2540 C->T No 2677 C -> T Yes 2975 C ->T Yes 3115 T->C Yes 3146 G->T Yes 3219 G->A Yes 3377 A->C Yes 3456 T-> C Yes 3611 G->T Yes 3718 A->G Yes 3785 C ->A Yes 3859 C -> T Yes 3862 G->C Yes 3870 T-> A Yes 3873 G -> C Yes 3875 C -> T Yes 4027 G->A Yes 4034 T -> C Yes WO 2005/072050 PCT/IB2005/000433 660 4115 C ->G Yes 4120 C ->T Yes 4129 G->T Yes 4130 G->C Yes 4226 G->A Yes 4232 C -> G Yes 4235 G->A Yes 4356 G->T Yes 4434 C->G Yes 4531 A->T Yes 4743 A -> C Yes 4813 C -> T Yes 4954 A->G Yes 4987 C -> T Yes 5143 A->G No 5235 T-> C Yes 5369 G -> No 5785 C -> G Yes 5996 G->C No 6039 G -> A Yes 6049 A -> C Yes 6224 A -> C Yes 6230 G -> A Yes 6295 A->C Yes Variant protein HSCOC4_PEA_1-P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T21. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or WO 2005/072050 PCT/IB2005/000433 more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4-PEA_1_P9 and CO4_RMANVl: 5 1.An isolated chimeric polypeptide encoding for HSCOC4_PEAlP9, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPINPGQRVRYRVFALDQKMRPSTDTITVMV 10 ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHSLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD 15 SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIV\FNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGELELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID 20 EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHILRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK 25 ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAFNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 30 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE

YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV

WO 2005/072050 PCT/IB2005/000433 662 HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHV'LL YFDSV corresponding to amino acids 1 - 1529 of C04_-HUMANV 1, which also corresponds to amino acids 1 - 1529 of HSCOC4_PEA_1 P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and 5 most preferably at least 95% homologous to a polypeptide having the sequence SGER corresponding to amino acids 1530 - 1533 of HSCOC4_PEA-lP9, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEALP9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER in HSCOC4-PEA_1_P9. It should be noted that the known protein sequence (CO4-HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino 15 acid sequence for C04_HUMANVi. These changes were previously known to occur and are listed in the table below. Table 31 - Changes to C04_HUMAN Vi SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072050 PCT/IB2005/000433 663 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Vafiant protein HSCOC4_PEA__P9 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 32, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 32 - Amino acid mutations SNP position s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L -> V Yes 183 G-> No 211 G -> No 322 A -> V No 322 A -> No 347 S -> Y Yes 423 Q-> No 478 P -> L Yes 549 H->P Yes 608 L -> V Yes 617 K->E Yes 726 P -> L Yes 872 V->A Yes 907 A -> T Yes 959 E->D Yes 1073 D -> G Yes 1120 P -> L Yes WO 2005/072050 PCT/IB2005/000433 664 1121 C -> S 1124 L -> I Yes 1125 D->H Yes 1176 S->N Yes 1207 A->V Yes 1210 R->L Yes 1286 A -> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No Variant protein HSCOC4-PEA_1_P9 is encoded by the following transcript(s): HSCOC4_PEAlT21, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T21 is shown in bold; this coding portion starts 5 at position 501 and ends at position 5099. The transcript also has the following SNPs as listed in Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4-PEAlP9 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 33 - Nucleic acid SNPs SNP position onnucleotide Alternative nucleic acid Previously known SNP? sequence 304 A->G Yes 884 G -> No 921 C -> G Yes 1049 C -> No 1131 G -> No 1465 C -> No 1465 C->T No WO 2005/072050 PCT/IB2005/000433 665 1517 C -> T Yes 1540 C -> A Yes 1768 A-> No 1778 C -> T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A -> C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G-> A Yes 2540 C ->T No 2677 C ->T Yes 2975 C -> T Yes 3115 T->C Yes 3146 G->T Yes 3219 G->A Yes 3377 A -> C Yes 3456 T-> C Yes 3611 G->T Yes 3718 A -> G Yes 3785 C -> A Yes 3859 C -> T Yes 3862 G -> C Yes 3870 T-> A Yes 3873 G -> C Yes 3875 C -> T Yes 4027 G -> A Yes 4034 T->C Yes 4115 C -> G Yes WO 2005/072050 PCT/IB2005/000433 666 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G -> A Yes 4356 G -> T Yes 4449 A->T Yes 4668 A -> G No 4760 T->C Yes 4894 G -> No 5561 G -> A Yes 6026 T -> G Yes 6348 G -> C Yes 6966 C -> G Yes 7177 G -> C No 7220 G -> A Yes 7230 A -> C Yes 7405 A -> C Yes 7411 G -> A Yes 7476 A -> C Yes Variant protein HSCOC4_PEA_1-P22 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T25. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 667 Comparison report between HSCOC4_PEA_1_P22 and CO4_HUMAN_V1: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P22, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR 5 NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHSLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 10 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG 15 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 20 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYDLDTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV 25 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL 30 YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC

SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAF

WO 2005/072050 PCT/IB2005/000433 668 RLFETKITQVLHF corresponding to amino acids I - 1653 of CO4-HUMAN-V1, which also corresponds to amino acids 1 - 1653 of HSCOC4_PEA-1_P22, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 SMKQTGEAGRAGGRQGG corresponding to amino acids 1654 - 1670 of HSCOC4-PEA_1_P22, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA-lP22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SMKQTGEAGRAGGRQGG in HSCOC4_PEAlP22. It should be noted that the known protein sequence (C04_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino 15 acid sequence for C04_HUMANVI. These changes were previously known to occur and are listed in the table below. Table 34 - Changes to C04_HUMAN_V1 SNP position(s) on Type of change 'amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072050 PCT/IB2005/000433 669 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P22 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 35, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAl_P22 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 35 -Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L->V Yes 183 G-> No 211 G -> No 322 A -> No 322 A -> V No 347 S -> Y Yes 423 Q-> No 478 P -> L Yes 549 H -> P Yes 608 L -> V Yes 617 K -> E Yes 726 P -> L Yes 872 V -> A Yes 907 A -> T Yes 959 E -> D Yes 1073 D -> G Yes 1120 P->L Yes WO 2005/072050 PCT/IB2005/000433 670 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S ->N Yes 1207 A->V Yes 1210 R->L Yes 1286 A-> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No 1604 R->G Yes Variant protein HSCOC4_PEA_1_P22 is encoded by the following transcript(s): HSCOC4_PEA_1_T25, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA__T25 is shown in bold; this coding portion starts 5 at position 501 and ends at position 5510. The transcript also has the following SNPs as listed in Table 36 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P22 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 36 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence, 304 A->G Yes 884 G -> No 921 C -> G Yes 1049 C -> No 1131 G -> No 1465 C-> No WO 2005/072050 PCT/IB2005/000433 671 1465 C->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C->T Yes 1933 C->T Yes 1985 C -> T Yes 2146 A->C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G->A Yes 2540 C -> T No 2677 C -> T Yes 2975 C -> T Yes 3115 T->C Yes 3146 G->T Yes 3219 G->A Yes 3377 A -> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C -> T Yes 3862 G -> C Yes 3870 T->A Yes 3873 G->C Yes 3875 C -> T Yes 4027 G -> A Yes 4034 T->C Yes WO 2005/072050 PCT/IB2005/000433 6'72 4115 C ->G Yes 4120 C ->T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G-> A Yes 4232 C -> G Yes 4235 G->A Yes 4356 G -> T Yes 4449 A -> T Yes 4668 A->G No 4760 T -> C Yes 4894 G-> No 5310 C -> G Yes 5783 G -> C No 5826 G->A Yes 5836 A -> C Yes 5974 C -> T Yes 5981 C -> T Yes 6154 A->C Yes 6160 G -> A Yes 6225 A -> C Yes 6283 C -> T Yes 6548 C -> T Yes 6567 C -> T Yes 7300 C -> A Yes 7520 C -> T Yes 7685 A -> C Yes WO 2005/072050 PCT/IB2005/000433 673 Variant protein HSCOC4_PEA_1_P23 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA-lT28. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or 5 more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4_PEAl-P23 and C04_HUM\/VAN_Vi: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA-lP23, comprising a 10 first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 15 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYN4LSRGQIVFMNREPKRTLTSVSVFVDHHLA 20 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL 25 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ 30 DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS

FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV

WO 2005/072050 PCT/IB2005/000433 674 TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV 5 HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYG corresponding to amino acids 1 - 1626 of C04_HUMANVI, which also corresponds to amino acids 1 - 1626 of HSCOC4_PEA_1_P23, and a second amino acid sequence being at least 70%, optionally at 10 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS corresponding to amino acids 1627 - 1685 of HSCOC4_PEA_1_P23, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of HSCOC4-PEA-lP23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS in 20 HSCOC4_PEA_1_P23. It should be noted that the known protein sequence (C04-HUMNAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04_HUMANVi. These changes were previously known to occur and are 25 listed in the table below. Table 37 - Changes to C04_HUMAN_V1 SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant WO 2005/072050 PCT/IB2005/000433 675 1208 variant 1211 variant 1287 variant The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 5 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure. Variant protein HSCOC4_PEA_1_P23 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 38, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4-PEA_1_P23 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 38 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 -> No 141 L -> V Yes 183 G-> No 211 G-> No 322 A -> V No 322 A -> No 347 S> Y Yes 423 Q-> No 478 P ->L Yes 549 H -> P Yes WO 2005/072050 PCT/IB2005/000433 676 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V->A Yes 907 A -> T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S -> N Yes 1207 A->V Yes 1210 R->L Yes 1286 A -> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No 1604 R->G Yes 1634 G -> Yes Variant protein HSCOC4_PEA__P23 is encoded by the following transcript(s): HSCOC4-PEAIT28, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T28 is shown in bold; this coding portion starts 5 at position 501 and ends at position 5555. The transcript also has the following SNPs as listed in Table 39 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P23 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 39 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 677 SNP pc :4"n on nucleotide Alternative nucleic acid Previously known SNP? Sequent( 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C -> A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A -> C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G-> A Yes 2540 C -> T No 2677 C -> T Yes 2975 C -> T Yes 3115 T-> C Yes 3146 G->T Yes 3219 G->A Yes 3377 A -> C Yes 3456 T->C Yes 3611 G -> T Yes WO 2005/072050 PCT/IB2005/000433 678 3718 A-> G Yes 3785 C -> A Yes 3859 C->T Yes 3862 G -> C Yes 3870 T->A Yes 3873 G -> C Yes 3875 C ->T Yes 4027 G -> A Yes 4034 T-> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G -> T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G-> A Yes 4356 G->T Yes 4449 A -> T Yes 4668 A -> G No 4760 T->C Yes 4894 G -> No 5310 C -> G Yes 5402 C -> Yes 5426 T->C Yes 5965 G-> C No 6008 G -> A Yes 6018 A -> C Yes 6156 C -> T Yes 6163 C -> T Yes 6336 A -> C Yes WO 2005/072050 PCT/IB2005/000433 679 6342 G-> A Yes 6407 A -> C Yes 6465 C ->T Yes 6730 C->T Yes 6749 C ->T Yes 7482 C -> A Yes 7702 C->T Yes 7867 A->C Yes Variant protein HSCOC4-PEA_1_P24 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T30. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P24 and C04_HUMAN-Vi: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA-lP24, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHSLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWTFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMLSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS

LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG

WO 2005/072050 PCT/IB2005/000433 680 LAFSDGDQW'LSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 5 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLA\TFQDEGAEPLKQRVEASISKASS 10 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV 15 HYTVCIVRNGKVGLSGMALADVTLLSGFHALRADLEKLTSLSDRYVSHETEGPHVLL YFDS corresponding to amino acids 1 - 1528 of C04_-HUMAN_Vi, which also corresponds to amino acids 1 - 1528 of HSCOC4_PEA_1_P24, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG corresponding to amino acids 1529 - 1579 of HSCOC4-PEAlP24, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P24, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG in HSCOC4_PEAl-P24. It should be noted that the known protein sequence (CO4_HUIAN) has one or more 30 changes than the sequence given at the end of the application and named as being the amino WO 2005/072050 PCT/IB2005/000433 681 acid sequence for C04-HUMAN_VI. These changes were previously known to occur and are listed in the table below. Table 40 - Changes to C04_HUMA4N_Vi SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P24 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 41, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P24 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 41 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L ->V Yes WO 2005/072050 PCT/IB2005/000433 682 183 G.> No 211 G-> No 322 A-> No 322 A->V No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V -> A Yes 907 A -> T Yes 959 E->D Yes 1073 D->G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S -> N Yes 1207 A->V Yes 1210 R->L Yes 1286 A -> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No 1569 S->R Yes Variant protein HSCOC4_PEA-lP24 is encoded by the following transcript(s): HSCOC4_PEA_1_T30, for which the sequence(s) is/are given at the end of the application. The WO 2005/072050 PCT/IB2005/000433 683 coding portion of transcript HSCOC4-PEAIT30 is shown in bold; this coding portion starts at position 501 and ends at position 5237. The transcript also has the following SNPs as listed in Table 42 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein HSCOC4_PEA_LP24 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 42 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? Sequence 304 A->G Yes 884 G-> No 21 C ->G Yes 1049 C-> No 1131 G-> No 465 C-> No 1465 C -> T No 1517 C -> T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A->C Yes 2162 G->A Yes 2322 C -> G Yes 2349 A ->G Yes 2435 G -> A Yes 2540 C -> T No 2677 C -> T Yes WO 2005/072050 PCT/IB2005/000433 684 2975 C ->T Yes 3115 T->C Yes 3146 G-> T Yes 3219 G-> A Yes 3377 A-> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C ->T Yes 3862 G -> C Yes 3870 T->A Yes 3873 G -> C Yes 3875 C ->T Yes 4027 G->A Yes 4034 T->C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G->C Yes 4226 G -> A Yes 4232 C -> G Yes 4235 G -> A Yes 4356 G->T Yes 4449 A->T Yes 4668 A -> G No 4760 T-> C Yes 4894 G-> No 5207 C -> G Yes 5418 G->C No WO 2005/072050 PCT/IB2005/000433 685 5461 G> A Yes 5471 A-> C Yes 5646 A> C Yes 5652 G> A Yes 5717 A C Yes Variant protein HSCOC4_PEA_1_P25 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4-PEA_1-T31. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P25 and C04-HUMAN_V 1: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA-lP25, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEfKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIRLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 25 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEED LID

EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL

WO 2005/072050 PCT/IB2005/000433 686 RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK 5 ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 10 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1 - 1593 of C04_HUMAN-VI, which also 15 corresponds to amino acids 1 - 1593 of HSCOC4_PEA_1_P25, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG corresponding to amino acids 1594 - 1657 of HSCOC4_PEA_1-P25, wherein said 20 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA&lP25, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG in HSCOC4_PEA_1_P25. It should be noted that the known protein sequence (C04_HUMAN) has one or more 30 changes than the sequence given at the end of the application and named as being the amino WO 2005/072050 PCT/IB2005/000433 687 acid sequence for CO4_HUMAN_V1. These changes were previously known to occur and are listed in the table below. Table 43 - Changes to C04_HUMAN_Vi SNP. position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P25 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 44, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 44 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L->V Yes WO 2005/072050 PCT/IB2005/000433 688 183 G-> No 211 G-> No 322 A-> No 322 A->V No 347 S->Y Yes 423 Q-> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V -> A Yes 907 A->T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D -> H Yes 1176 S -> N Yes 1207 A-> V Yes 1210 R->L Yes 1286 A-> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No 1632 A-> G Yes Variant protein HSCOC4-PEA__P25 is encoded by the following transcript(s): HSCOC4PEAlT3 1, for which the sequence(s) is/are given at the end of the application. The WO 2005/072050 PCT/IB2005/000433 689 coding portion of transcript HSCOC4_PEAlT31 is shown in bold; this coding portion starts at position 501 and ends at position 5471. The transcript also has the following SNPs as listed in Table 45 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein HSCOC4_PEA_1_P25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 45 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Pteviously known SNP? sequence 304 A-> G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C -> No 1465 C->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A ->G Yes 2435 G-> A Yes 2540 C -> T No 2677 C -> T Yes WO 2005/072050 PCT/IB2005/000433 690 2975 C -> T Yes 3115 T->C Yes 3146 G->T Yes 3219 G -> A Yes 3377 A -> C Yes 3456 T->C Yes 3611 G -> T Yes 3718 A->G Yes 3785 C -> A Yes 3859 C->T Yes 3862 G -> C Yes 3870 T->A Yes 3873 G -> C Yes 3875 C -> T Yes 4027 G -> A Yes 4034 T->C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G->A Yes 4232 C -> G Yes 4235 G->A Yes 4356 G->T Yes 4449 A->T Yes 4668 A -> G No 4760 T -> C Yes 4894 G -> No 5395 C -> G Yes 5606 G -> C No WO 2005/072050 PCT/IB2005/000433 691 5649 G-> A Yes 5659 A-> C Yes 5834 A-> C Yes 5840 G->A Yes 5905 A-> C Yes Variant protein HSCOC4_PEA_1_P26 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA-_T32. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA__P26 and C04_HUMAN-VI: 1.An isolated chimeric polypeptide encoding for HSCOC4-PEA_1_P26, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAY\RFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNM1GITDLQ GLRLYVAAAHESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHL A PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 25 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID

EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL

WO 2005/072050 PCT/IB2005/000433 692 RVFREFHLHLRLPMSVRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRQQFRK 5 ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 10 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1 - 1593 of C04_HUMAN-V 1, which also 15 corresponds to amino acids 1 - 1593 of HSCOC4_PEA_1_P26, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL corresponding to amino acids 20 1594 - 1691 of HSCOC4_PEA_1_P26, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA-lP26, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL in HSCOC4_PEA_1_P26. It should be noted that the known protein sequence (C04-HUMAN) has one or more 30 changes than the sequence given at the end of the application and named as being the amino WO 2005/072050 PCT/IB2005/000433 693 acid sequence for C04-HIUMANV1. These changes were previously known to occur and are listed in the table below. Table 46 - Changes to C04_HUMAN_Vi SNP positions) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA-1_P26 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 47, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P26 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 47 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q .> No 141 L->V Yes WO 2005/072050 PCT/IB2005/000433 694 183 G-> No 211 G-> No 322 A-> No 322 A ->V No 347 S ->Y Yes 423 Q-> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V -> A Yes 907 A->T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D -> H Yes 1176 S ->N Yes 1207 A->V Yes 1210 R->L Yes 1286 A-> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No 1632 A -> G Yes 1663 P -> Yes 1671 C -> R Yes WO 2005/072050 PCT/IB2005/000433 695 Variant protein HSCOC4-PEA_1_P26 is encoded by the following transcript(s): HSCOC4_PEA-1-T32, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4-PEA-lT32 is shown in bold; this coding portion starts at position 501 and ends at position 5573. The transcript also has the following SNPs as listed in 5 Table 48 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4-PEA-_LP26 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 48 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G->A Yes 2322 C-> G Yes 2349 A-> G Yes 2435G A Yes WO 2005/072050 PCT/IB2005/000433 696 2540 C ->T No 2677 C T Yes 2975 C -> T Yes 3115 T->C Yes 3146 G->T Yes 3219 G->A Yes 3377 A-> C Yes 3456 T-> C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C -> T Yes 3862 G -> C Yes 3870 T->A Yes 3873 G -> C Yes 3875 C->T Yes 4027 G -> A Yes 4034 T-> C Yes 4115 C->G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G-> A Yes 4232 C -> G Yes 4235 G->A Yes 4356 G -> T Yes 4449 A->T Yes 4668 A -> G No 4760 T -> C Yes 4894 G -> No WO 2005/072050 PCT/IB2005/000433 697 5395 C ->G Yes 5487 C> Yes 5511 T->C Yes 6050 G-> C No 6093 G -> A Yes 6103 A->C Yes 6278 A-> C Yes 6284 G-> A Yes 6349 A -> C Yes 6407 C -> T Yes 6672 C -> T Yes 6691 C -> T Yes 7424 C -> A Yes 7644 C -> T Yes 7809 A -> C Yes Variant protein HSCOC4_PEA_1_P30 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T40. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA-1_P30 and C04_-HUMANV3 (SEQ ID NO: 487): 1.An isolated chimeric polypeptide encoding for HSCOC4_PEAlP30, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR 15 NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK WO 2005/072050 PCT/IB2005/000433 698 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE 5 LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKR.TLTSVSVFVDHHI-LA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKTFEAMNSYDLGCGPGGGDSALQVFQAAG 10 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL 15 VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 20 corresponding to amino acids 1 - 1232 of C04_HUMANV3, which also corresponds to amino acids 1 - 1232 of HSCOC4_PEA_1_P30, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RNPVRLLQPRAQMFCVLRGTK corresponding to amino acids 1233 - 1253 of 25 HSCOC4_PEA-l-P30, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P30, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 30 sequence RNPVRLLQPRAQMFCVLRGTK in HSCOC4_PEA_1_P30.

WO 2005/072050 PCT/IB2005/000433 699 It should be noted that the known protein sequence (CO4_HUMANS) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04_HUMANV3. These changes were previously known to occur and are listed in the table below. 5 Table 49 - Changes to C04_HUMAN_V3 SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 vacant 1211 variant The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P30 also has the following non-silent SNPs (Single 15 Nucleotide Polymorphisms) as listed in Table 50, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P30 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 50 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP7 sequence 128 Q-> No WO 2005/072050 PCT/IB2005/000433 700 141 L->V Yes 183 G -> No 211 G -> No 322 A -> No 322 A->V No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V->A Yes 907 A->T Yes 959 E->D Yes 1073 D->G Yes 1120 P->L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D->H Yes 1176 S -> N Yes 1207 A -> V Yes 1210 R->L Yes Variant protein HSCOC4_PEA_1_P30 is encoded by the following transcript(s): HSCOC4-PEAlT40, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T40 is shown in bold; this coding portion starts 5 at position 501 and ends at position 4259. The transcript also has the following SNPs as listed in Table 51 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of WO 2005/072050 PCT/IB2005/000433 701 known SNPs in variant protein HSCOC4_PEAlP30 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 51 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A -> G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C -> T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G -> A Yes 2540 C->T No 2677 C -> T Yes 2975 C ->T Yes 3115 T->C Yes 3146 G ->T Yes 3219 G ->A Yes WO 2005/072050 PCT/IB2005/000433 702 3377 A-> C Yes 3456 T->C Yes 3611 G -> T Yes 3718 A-> G Yes 3785 C ->A Yes 3859 C -> T Yes 3862 G->C Yes 3870 T->A Yes 3873 G->C Yes 3875 C->T Yes 4027 G -> A Yes 4034 T -> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G-> C Yes 4348 C -> G Yes 4559 G -> C No 4602 G -> A Yes 4612 A -> C Yes 4787 A-> C Yes 4793 G->A Yes 4858 A -> C Yes Variant protein HSCOC4_PEA_1_P38 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T2. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief WO 2005/072050 PCT/IB2005/000433 703 description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSCOC4_PEA_1_P38 and C04-HUMAN: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1-P38, comprising a 5 first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 10 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA 15 PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMvNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding 20 to amino acids 1 - 818 of C04_HUMAN, which also corresponds to amino acids 1 - 818 of HSCOC4_PEA-lP38, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS corresponding to amino acids 819 - 843 of HSCOC4_PEA_1 P38, wherein said first amino acid 25 sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P38, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS in HSCOC4_PEA-1_P38. 30 WO 2005/072050 PCT/IB2005/000433 704 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P38 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 52, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P38 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 52 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L-> V Yes 183 G -> No 211 G-> No 322 A-> No 322 A ->V No 347 S ->Y Yes 423 Q-> No 478 P ->L Yes 549 H ->P Yes 608 L-> V Yes 617 K -> E Yes 726 P->L Yes 829 L->P Yes WO 2005/072050 PCT/IB2005/000433 705 830 L->I Yes 840 S -> P Yes The glycosylation sites of variant protein HSCOC4_PEA_1_P38, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 53 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 53 - Glycosylation site(s) Position(s) on. known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 no 226 yes 226 1328 no The phosphorylation sites of variant protein HSCOC4_PEA_1_P38, as compared to the 10 known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 54 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 54 - Phosphotylation sites) Position(s) on known amino Present in variant protein? acid sequence 1420 no 1422 no 1417 no 15 WO 2005/072050 PCT/IB2005/000433 706 Variant protein HSCOC4_PEA_1_P38 is encoded by the following transcript(s): HSCOC4_PEA_1_T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T2 is shown in bold; this coding portion starts at position 501 and ends at position 3029. The transcript also has the following SNPs as listed in 5 Table 55 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP38 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 55 - Nucleic acid SNPs SNP position onnucleotide Alternative nucleic acid Previously known SNP? sequence, 304 A ->G Yes 884 G-> No 921 C -> G Yes 1049 C-> No 1131 G-> No 1465 C-> No 1465 C -> T No 1517 C ->T Yes 1540 C -> A Yes 1768 A-> No 1778 C ->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A ->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G -> A Yes WO 2005/072050 PCT/IB2005/000433 707 2540 C->T No 2677 C -> T Yes 2986 T->C Yes 2988 C ->A Yes 3018 T-> C Yes 3070 C -> T Yes 3081 C->A Yes 3093 A -> G Yes 3101 G -> A Yes 3106 G -> A Yes 3174 G -> A Yes 3193 A -> G Yes 3201 T -> C Yes 3233 C -> T Yes 3373 T-> C Yes 3404 G -> T Yes 3477 G -> A Yes 3635 A -> C Yes 3714 T->C Yes 3869 G -> T Yes 3976 A->G Yes 4043 C -> A Yes 4117 C -> T Yes 4120 G -> C Yes 4128 T->A Yes 4131 G -> C Yes 4133 C -> T Yes 4285 G->A Yes 4292 T-> C Yes 4373 C -> G Yes WO 2005/072050 PCT/IB2005/000433 708 4378 C ->T Yes 4387 G-> T Yes 4388 G->C Yes 4484 G -> A Yes 4490 C -> G Yes 4493 G->A Yes 4614 G->T Yes 4707 A -> T Yes 4926 A->G No 5018 T->C Yes 5152 G-> No 5568 C -> G Yes 5779 G->C No 5822 G -> A Yes 5832 A -> C Yes 6007 A -> C Yes 6013 G->A Yes 6078 A -> C Yes Variant protein HSCOC4_PEA_1_P39 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T5. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P39 and C04_HUMAN: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P39, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072050 PCT/IB2005/000433 709 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL 5 PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ corresponding to amino acids 1 - 387 of C04_HUIMAN, which also corresponds to amino acids 1 - 387 of HSCOC4_PEA_1 P39, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, 10 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSSRGEG corresponding to amino acids 388 - 394 of HSCOC4_PEAlP39, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_lP39, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSSRGEG in HSCOC4_PEA_1_P39. The location of the variant protein was determined according to results from a number of 20 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans- membrane region. 25 Variant protein HSCOC4_PEA_1_P39 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 56, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP39 sequence provides support for the deduced sequence of this variant protein according to the 30 present invention).

WO 2005/072050 PCT/IB2005/000433 710 Table 56 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L->V Yes 183 G -> No 211 G-> No 322 A-> No 322 A-> V No 347 S->Y Yes The glycosylation sites of variant protein HSCOC4_PEA_1_P39, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 5 57 (given according to their position(s) on the amino acid sequene in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 57 - Glycosylation sitess) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 no 226 yes 226 1328 no 10 The phosphorylation sites of variant protein HSCOC4_PEA_1_P39, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 58 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

WO 2005/072050 PCT/IB2005/000433 711 Table 58 - Phosphoiylation sites) Position(s) on known amino Present in variant protein? acid sequence 1420 no 1422 no 1417 no Variant protein HSCOC4_PEA_1_P39 is encoded by the following transcript(s): HSCOC4_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The 5 coding portion of transcript HSCOC4_PEAl-T5 is shown in bold; this coding portion starts at position 501 and ends at position 1682. The transcript also has the following SNPs as listed in Table 59 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP39 sequence provides support for the 10 deduced sequence of this variant protein according to the present invention). Table 59 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A ->G Yes 884 G No 921 C->G Yes 1049 C-> No 1131 G-> No 1465 C -> No 1465 C -> T No 1517 C -> T Yes 1540 C -> A Yes 1742 C ->A Yes 1756 C ->A Yes WO 2005/072050 PCT/IB2005/000433 712 1867 A-> No 1877 C -> T Yes 2032 C->T Yes 2084 C -> T Yes 2245 A ->C Yes 2261 G->A Yes 2421 C -> G Yes 2448 A -> G Yes 2534 G->A Yes 2639 C -> T No 2776 C->T Yes 3074 C -> T Yes 3214 T->C Yes 3245 G -> T Yes 3318 G->A Yes 3476 A->C Yes 3555 T->C Yes 3710 G->T Yes 3817 A -> G Yes 3884 C->A Yes 3958 C -> T Yes 3961 G -> C Yes 3969 T-> A Yes 3972 G -> C Yes 3974 C -> T Yes 4126 G->A Yes 4133 T->C Yes 4214 C -> G Yes 4219 C -> T Yes 4228 G->T Yes WO 2005/072050 PCT/IB2005/000433 713 4229 G-> C Yes 4325 G->A Yes 4331 C ->G Yes 4334 G-> A Yes 4455 G -> T Yes 4548 A->T Yes 4767 A-> G No 4859 T-> C Yes 4993 G-> No 5409 C -> G Yes 5620 G -> C No 5663 G -> A Yes 5673 A-> C Yes 5848 A -> C Yes 5854 G->A Yes 5919 A -> C Yes Variant protein HSCOC4_PEA_1_P40 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA-lT7. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P40 and C04-HUMAN: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA.lP40, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR

NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK

WO 2005/072050 PCT/IB2005/000433 714 DSLSRTTNIQGINLLSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY corresponding to amino acids 1 - 236 of C04_HUMAN, which also corresponds to amino acids 1 - 236 of HSCOC4_PEA-_LP40, and a second amino acid sequence being at least 70%, 5 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY corresponding to amino acids 237 - 263 of HSCOC4_PEAlP40, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 2.An isolated polypeptide encoding for a tail of HSCOC4_PEAlP40, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AGEWTEPHFPLKGRVPGRPGEAEYGIY in HSCOC4_PEA_1_P40. 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 20 region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEAlP40 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 60, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P40 25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 60 - Anino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q- No WO 2005/072050 PCT/IB2005/000433 715 141 L->V Yes 183 G -> No 211 G-> No 254 R-> No The glycosylation sites of variant protein HSCOC4_PEA_1_P40, as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 61 (given according to their position(s) on the amino acid sequence in the first column; the 5 second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 61 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 1391 no 862 no 226 yes 226 1328 no The phosphorylation sites of variant protein HSCOC4_PEA_1_P40, as compared to the 10 known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 62 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 62 - Phosphoiylation sites) Posit ion(s) on known amino Present in variant protein? acid sequence 1420 no 1422 no 1417 no WO 2005/072050 PCT/IB2005/000433 716 Variant protein HSCOC4_PEA_1_P40 is encoded by the following transcript(s): HSCOC4_PEAl-T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T7 is shown in bold; this coding portion starts at 5 position 501 and ends at position 1289. The transcript also has the following SNPs as listed in Table 63 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP40 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 63 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A ->G Yes 884 G-> No 921 C ->G Yes 1049 C-> No 1131 G -> No 1262 C -> No 1262 C->T No 1314 C ->T Yes 1337 C ->A Yes 1565 A-> No 1575 C->T Yes 1730 C->T Yes 1782 C ->T Yes 1943 A -> C Yes 1959 G -> A Yes 2119 C ->G Yes 2146 A ->G Yes WO 2005/072050 PCT/IB2005/000433 717 2232 G A Yes 2337 C -> T No 2474 C -> T Yes 2772 C -> T Yes 2912 T -> C Yes 2943 G -> T Yes 3016 G->A Yes 3174 A -> C Yes 3253 T->C Yes 3408 G -> T Yes 3515 A -> G Yes 3582 C -> A Yes 3656 C -> T Yes 3659 G->C Yes 3667 T->A Yes 3670 G -> C Yes 3672 C -> T Yes 3824 G -> A Yes 3831 T->C Yes 3912 C -> G Yes 3917 C -> T Yes 3926 G -> T Yes 3927 G -> C Yes 4023 G -> A Yes 4029 C -> G Yes 4032 G->A Yes 4153 G->T Yes 4246 A->T Yes 4465 A -> G No 4557 T->C Yes WO 2005/072050 PCT/IB2005/000433 718 4691 G-> No 5107 C ->G Yes 5318 G ->C No 5361 G ->A Yes 5371 A ->C Yes 5546 A ->C Yes 5552 G->A Yes 5617 A -> C Yes Variant protein HSCOC4_PEA-1-P41 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T8. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4_PEA_1_P41 and C04-HUMAN-Vi: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P41, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGP GFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDIHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS

LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG

WO 2005/072050 PCT/IB2005/000433 719 LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ 5 QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDIIAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS 10 FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV 15 HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1 - 1529 of C04_HUMAN_VI, which also corresponds to amino acids 1 - 1529 of HSCOC4_PEA_1_P41, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER 20 corresponding to amino acids 1530 - 1533 of HSCOC4_PEA_1_P41, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HSCOC4_PEA_1_P41, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence SGER in HSCOC4_PEAl-P41. It should be noted that the known protein sequence (C04-HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for C04_HUMvJANV 1. These changes were previously known to occur and are 30 listed in the table below.

WO 2005/072050 PCT/IB2005/000433 720 Table 64 - Changes to CO4_HUMAN_Vi SNP position(s) on Type of change amino acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure. Variant protein HSCOC4_PEA_1_P41 also has the following non-silent SNPs (Single 10 Nucleotide Polymorphisms) as listed in Table 65, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P41 sequence provides support for the deduced sequence of this variant protein according to the present invention). 15 Table 65 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 128 Q-> No 141 L ->V Yes 183 G-> No WO 2005/072050 PCT/IB2005/000433 721 211 G-> No 322 A->V No 322 A-> No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H->P Yes 608 L->V Yes 617 K->E Yes 726 P->L Yes 872 V -> A Yes 907 A->T Yes 959 E->D Yes 1073 D -> G Yes 1120 P->L Yes 1121 C->S Yes 1124 L->I Yes 1125 D -> H Yes 1176 S -> N Yes 1207 A -> V Yes 1210 R-> L Yes 1286 A->S Yes 1317 I->F Yes 1390 K.->E No 1465 R-> No Variant protein HSCOC4_PEA_1_P41 is encoded by the following transcript(s): HSCOC4_PEA_1_T8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_1_T8 is shown in bold; this coding portion starts at 5 position 501 and ends at position 5099. The transcript also has the following SNPs as listed in WO 2005/072050 PCT/IB2005/000433 722 Table 66 (given according to their position on ':he nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAlP41 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 66 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A-> G Yes 884 G -> No 921 C -> G Yes 1049 C -> No 1131 G -> No 1465 C -> No 1465 C ->T No 1517 C ->T Yes 1540 C ->A Yes 1768 A-> No 1778 C->T Yes 1933 C ->T Yes 1985 C ->T Yes 2146 A->C Yes 2162 G-> A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G-> A Yes 2540 C->T No 2677 C -> T Yes 2975 C -> T Yes 3115 T-> C Yes WO 2005/072050 PCT/IB2005/000433 723 3146 G -> T Yes 3219 G->A Yes 3377 A-> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A-> G Yes 3785 C -> A Yes 3859 C ->T Yes 3862 G->C Yes 3870 T->A Yes 3873 G-> C Yes 3875 C ->T Yes 4027 G -> A Yes 4034 T -> C Yes 4115 C->G Yes 4120 C ->T Yes 4129 G->T Yes 4130 G->C Yes 4226 G->A Yes 4232 C -> G Yes 4235 G-> A Yes 4356 G->T Yes 4449 A -> T Yes 4668 A->G No 4760 T->C Yes 4894 G -> No 5561 G->A Yes 6026 T -> G Yes 6348 G -> C Yes 6801 C -> G Yes WO 2005/072050 PCT/IB2005/000433 724 7012 G-> C No 7055 G-> A Yes 7065 A -> C Yes 7240 A -> C Yes 7246 G->A Yes 7311 A-> C Yes Variant protein HSCOC4_PEA-1_P42 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HSCOC4_PEA_1_T12. An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HSCOC4-PEA_1_P42 and C04-HUMAN_VI: 1.An isolated chimeric polypeptide encoding for HSCOC4_PEA_1_P42, comprising a first amino acid sequence being at least 90 % homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK 15 DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQK.MRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP 20 EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR 25 LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID WO 2005/072050 PCT/IB2005/000433 725 EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARCSFEFPVGDAVSKVLQIEKEGAIHREEL VYTLNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL 5 LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR 10 QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIW corresponding to amino acids 1 - 1473 of C04_HUIMANVI, which also corresponds to amino acids 1 - 1473 of HSCOC4_PEA_1-P42, a second amino acid sequence 15 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR corresponding to amino acids 1474 - 1511 of HSCOC4_PEA_1_P42, a third amino acid sequence being at least 90 % homologous to RNGKVGLSGMALkDVTLLSGFHALRADLEK corresponding to amino acids 20 1474 - 1503 of C04-HUMANV1, which also corresponds to amino acids 1512 - 1541 of HSCOC4_PEA_1_P42, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWSATQGNPLCPRY corresponding to amino acids 1542 - 1555 of HSCOC4_PEA_1_P42, wherein said first amino acid sequence, 25 second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of HSCOC4_PEA_lP42, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% 30 homologous to the sequence encoding for WO 2005/072050 PCT/IB2005/000433 726 WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR, corresponding to HSCOC4_PEA_1_P42. 3.An isolated polypeptide encoding for a tail of HSCOC4_PEA_P42, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWSATQGNPLCPRY in HSCOC4_PEA_1_P42. It should be noted that the known protein sequence (C04_HUJMAN) has one or more changes than the sequence given at the end of the application and named as being the amino 10 acid sequence for CO4_HUMAN_V1. These changes were previously known to occur and are listed in the table below. Table 67 - Changes to C04_HUMAN_V1 SNP position(s) on Type of change amino, acid sequence 1177 variant 1202 variant 1208 variant 1211 variant 1287 variant 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 20 region prediction program predicts that this protein has a trans-membrane region. Variant protein HSCOC4_PEA_1_P42 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 68, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether WO 2005/072050 PCT/IB2005/000433 727 the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_1_P42 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 68 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence. 128 Q-> No 141 L -> V Yes 183 G-> No 211 G-> No 322 A -> V No 322 A -> No 347 S -> Y Yes 423 Q -> No 478 P->L Yes 549 H -> P Yes 608 L-> V Yes 617 K -> E Yes 726 P->L Yes 872 V -> A Yes 907 A -> T Yes 959 E -> D Yes 1073 D -> G Yes 1120 P -> L Yes 1121 C -> S Yes 1124 L->I Yes 1125 D -> H Yes 1176 S -> N Yes 1207 A-> V Yes WO 2005/072050 PCT/IB2005/000433 728 1210 R->L Yes 1286 A-> S Yes 1317 I->F Yes 1390 K->E No 1465 R-> No Variant protein HSCOC4_PEA_1_P42 is encoded by the following transcript(s): HSCOC4_PEA_1_T12, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA_-T12 is shown in bold; this coding portion starts 5 at position 501 and ends at position 5165. The transcript also has the following SNPs as listed in Table 69 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEAl-P42 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 69 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 304 A -> G Yes 884 G -> No 921 C ->G Yes 1049 C-> No 1131 G.> No 1465 C -> No 1465 C ->T No 1517 C -> T Yes 1540 C -> A Yes 1768 A -> No 1778 C -> T Yes 1933 C -> T Yes WO 2005/072050 PCT/IB2005/000433 72 9 1985 C ->T Yes 2146 A->C Yes 2162 G ->A Yes 2322 C -> G Yes 2349 A -> G Yes 2435 G -> A Yes 2540 C->T No 2677 C -> T Yes 2975 C -> T Yes 3115 T->C Yes 3146 G->T Yes 3219 G -> A Yes 3377 A -> C Yes 3456 T->C Yes 3611 G->T Yes 3718 A -> G Yes 3785 C -> A Yes 3859 C -> T Yes 3862 G -> C Yes 3870 T-> A Yes 3873 G -> C Yes 3875 C -> T Yes 4027 G -> A Yes 4034 T-> C Yes 4115 C -> G Yes 4120 C -> T Yes 4129 G->T Yes 4130 G -> C Yes 4226 G -> A Yes 4232 C -> G Yes WO 2005/072050 PCT/IB2005/000433 730 4235 G -> A Yes 4356 G->T Yes 4449 A->T Yes 4668 A-> G No 4760 T-> C Yes 4894 G -> No 5765 G -> A Yes 6230 T-> G Yes 6552. G -> C Yes 7005 C -> G Yes 7216 G->C No 7259 G->A Yes 7269 A -> C Yes 7444 A -> C Yes 7450 G -> A Yes 7515 A -> C Yes As noted above, cluster HSCOC4 features 79 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster HSCOC4_PEA_1_nodeI according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, 10 HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4-PEA_1_T4, HSCOC4_PEA_1_T5, HSCOC4-PEA_1-T7, HSCOC4_PEA_1_TS, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEAlT25, HSCOC4_PEA_1_T28, HSCOC4_PEA-lT30, HSCOC4_PEA_1_T3 1, HSCOC4_PEA_1_T32 and WO 2005/072050 PCT/IB2005/000433 731 HSCOC4_PEA-lT40. Table 70 below describes the starting and ending position of this segment on each transcript. Table 70 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 1 535 HSCOC4_PEA 1 T2 1 535 HSCOC4_PEA 1_T3 1 535 HSCOC4_PEA_1 T4 1 535 HSCOC4_PEA-lT5 1 535 HSCOC4_PEA 1 T7 1 535 HSCOC4_PEA-1-T8 1 535 HSCOC4_PEA-1_TI 1 535 HSCOC4-PEA 1_T12 1 535 HSCOC4_PEAI T14 1 535 HSCOC4_PEA_1 15 1 535 HSCOC4-PEA_1_T20 1 535 HSCOC4_PEA_1T21 1 535 HSCOC4_PEA_1_T25 1 535 HSCOC4_PEA_1_T28 1 535 HSCOC4_PEA_1_T30 1 535 HSCOC4_PEA_1_T31 1 535 HSCOC4-PEA_1_T32 1 535 HSCOC4_PEAlT40 1 535 5 Segment cluster HSCOC4_PEA_1_node_5 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4-PEAl-T2, HSCOC4-PEA_1T3, HSCOC4_PEA1 1T4, HSCOC4_PEA_1_T5, WO 2005/072050 PCT/IB2005/000433 732 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA-_11, HSCOC4-PEAI_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1T15, HSCOC4_PEA_1_T20, HSCOC4_PEA-lT21, HSCOC4_PEAl-T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1T30, HSCOC4-PEAlT31, HSCOC4_PEAIT32 and 5 HSCOC4_PEA_1_T40. Table 71 below describes the starting and ending position of this segment on each transcript. Table 71 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_TI 566 764 HSCOC4_PEA_1T2 566 764 HSCOC4_PEA_1T3 566 764 HSCOC4-PEAl-T4 566 764 HSCOC4_PEA_1T5 566 764 HSCOC4_PEA_1 T7 566 764 HSCOC4_PEA-lT8 566 764 HSCOC4_PEA_1_T11 566 764 HSCOC4_PEA-_1 T12 566 764 HSCOC4_PEA1_-T14 566 764 HSCOC4_PEA_1_15 566 764 HSCOC4_PEA_1_T20 566 764 HSCOC4_PEAl-T21 566 764 HSCOC4_PEA-lT25 566 764 HSCOC4_PEA_1_T28 566 764 HSCOC4-PEA-lT30 566 764 HSCOC4_PEA_1_T31 566 764 HSCOC4_PEA_1_T32 566 764 HSCOC4_PEA_1_T40 566 764 WO 2005/072050 PCT/IB2005/000433 733 Segment cluster HSCOC4_PEA_1_node_7 according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4-PEA_1_T2, HSCOC4_PEA-1-T3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, 5 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA-1_TIl , HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1T15, HSCOC4_PEA_1_T20, HSCOC4-PEA_1_T21, HSCOC4-PEAI-T25, HSCOC4_PEA-lT28, HSCOC4_PEA1 1T30, HSCOC4_PEA-lT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 72 below describes the starting and ending position of this 10 segment on each transcript. Table 72 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1TI 765 885 HSCOC4_PEA_1_T2 765 885 HSCOC4_PEA 1T3 765 885 HSCOC4_PEA__T4 765 885 HSCOC4_PEA 1T5 765 885 HSCOC4_PEA_1_T7 765 885 HSCOC4_PEA_1 T8 765 885 HSCOC4_PEA_1_T1l 765 885 HSCOC4_PEA_1_12 765 885 HSCOC4_PEA 1 14 765 885 HSCOC4_PEA_1_15 765 885 HSCOC4_PEA_1 T20 765 885 HSCOC4_PEA lT21 765 885 HSCOC4_PEA 1T25 765 885 HSCOC4_PEA_1_T28 765 885 HSCOC4_PEA_1_T30 765 885 WO 2005/072050 PCT/IB2005/000433 734 HSCOC4_PEAIT31 765 885 HSCOC4_PEAl-T32 765 885 HSCOC4_PEA_1_T40 765 885 Segment cluster HSCOC4_PEA_1_node_30 according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1-Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1T4, HSCOC4_PEA_1-T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1 T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA-1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA__T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1-T30, HSCOC4_PEA_1-T31, HSCOC4_PEA_1_T32 and HSCOC4_PEAIT40. Table 73 below describes the starting and ending position of this segment on each transcript. Table 73 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 1662 1841 HSCOC4_PEA_1_T2 1662 1841 HSCOC4_PEA_1_T3 1662 1841 HSCOC4_PEAlT4 1662 1841 HSCOC4_PEA_1_T5 1761 1940 HSCOC4_PEA__T7 1459 1638 HSCOC4_PEA_1_T8 1662 1841 HSCOC4_PEA_Tl1 1662 1841 HSCOC4_PEA_1_T12 1662 1841 HSCOC4_PEA_1_14 1662 1841 HSCOC4_PEA115 1662 1841 WO 2005/072050 PCT/IB2005/000433 735 HSCOC4_PEA_1_T20 1662 1841 HSCOC4_PEA_1_T21 1662 1841 HSCOC4_PEA_1_T25 1662 1841 HSCOC4_PEA_1_T28 1662 1841 HSCOC4_PEAIT30 1662 1841 HSCOC4_PEA_-T31 1662 1841 HSCOC4_PEA_1_T32 1662 1841 HSCOC4_PEA-lT40 1662 1841 Segment cluster HSCOC4_PEAInode_33 according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEAIT3, HSCOC4_PEA_-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA-lT7, HSCOC4_PEA-lT8, HSCOC4_PEA_1_TIl, HSCOC4_PEA_1_T12, HSCOC4-PEA_1_T14, HSCOC4_PEA_1-T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1_T30, HSCOC4_PEA-lT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 74 below describes the starting and ending position of this segment on each transcript. Table 74 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 1842 2024 HSCOC4_PEA_1_T2 1842 2024 HSCOC4_PEA 1 T3 1842 2024 HSCOC4_PEA1 _T4 1842 2024 HSCOC4_PEA_1_T5 1941 2123 HSCOC4_PEA-_T7 1639 1821 WO 2005/072050 PCT/IB2005/000433 736 HSCOC4_PEA 1 TS 1842 2024 HSCOC4_PEA 1 T 1l 1842 2024 HSCOC4_PEA 1 12 1842 2024 HSCOC4_PEA_1_T14 1842 2024 HSCOC4_PEA_1 T15 1842 2024 HSCOC4_PEA 1_T20 1842 2024 HSCOC4_PEA 1 T21 1842 2024 HSCOC4_PEA 1 T25 1842 2024 HSCOC4_PEA_1_T28 1842 2024 HSCOC4_PEA-1-T30 1842 2024 HSCOC4_PEA_1T31 1842 2024 HSCOC4_PEA_1_T32 1842 2024 HSCOC4_PEA_1_T40 1842 2024 Segment cluster HSCOC4_PEA_1-node_35 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_T1, HSCOC4_PEA_1T2, HSCOC4_PEA-lT3, HSCOC4_PEA-1 T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1T7, HSCOC4PEA-1-T8, HSCOC4_PEA_1_T 1, HSCOC4_PEA_1_12, HSCOC4_PEA-_1T14, HSCOC4_PEA-1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1T21, HSCOC4PEAJlT25, HSCOC4_PEA_1_T28, 10 HSCOC4-PEA_1-T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 75 below describes the starting and ending position of this segment on each transcript. Table 75 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_TI 2025 2210 WO 2005/072050 PCT/IB2005/000433 737 HSCOC4_PEA_1-T2 2025 2210 HSCOC4_PEAI-T3 2025 2210 HSCOC4_PEA_1_T4 2025 2210 HSCOC4-PEA-lT5 2124 2309 HSCOC4-PEA-lT7 1822 2007 HSCOC4_PEA_1_TS 2025 2210 HSCOC4_PEA 1 TIl 2025 2210 HSCOC4_PEA_1_12 2025 2210 HSCOC4_PEA1 _T14 2025 2210 HSCOC4_PEA_1 15 2025 2210 HSCOC4_PEA lT20 2025 2210 HSCOC4_PEA lT21 2025 2210 HSCOC4-PEA_1T25 2025 2210 HSCOC4_PEA1 T28 2025 2210 HSCOC4_PEA_1T30 2025 2210 HSCOC4_PEA_1_T31 2025 2210 HSCOC4_PEAl-T32 2025 2210 HSCOC4_PEA1 T40 2025 2210 Segment cluster HSCOC4_PEA_1_node_37 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_1, HSCOC4_PEA_1T2, HSCOC4_PEA_1T3, HSCOC4_PEAl-T4, HSCOC4_PEAlT5, HSCOC4_PEA_1T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_T1l, HSCOC4_PEA_1_12, HSCOC4_PEA-_1T14, HSCOC4-PEA_115, HSCOC4_PEA_1_T20, HSCOC4_PEA-l_T21, HSCOC4_PEA_1_T25, HSCOC4-PEA_1_T28, 10 HSCOC4_PEAlT30, HSCOC4_PEA_1T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 76 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 738 Table 76 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_Ti 2211 2369 HSCOC4_PEA 1_T2 2211 2369 HSCOC4_PEA 1_T3 2211 2369 HSCOC4_PEA 1 T4 2211 2369 HSCOC4_PEA 1_T5 2310 2468 HSCOC4_PEA 1 T7 2008 2166 HSCOC4_PEAI 1T8 2211 2369 HSCOC4PEA1Tl 2211 2369 HSCOC4_PEA_1 T12 2211 2369 HSCOC4_PEA 1 T14 2211 2369 HSCOC4_PEAI_T15 2211 2369 HSCOC4_PEA lT20 2211 2369 HSCOC4_PEA 1 T21 2211 2369 HSCOC4_PEA I T25 2211 2369 HSCOC4_PEA_1 T28 2211 2369 HSCOC4_PEA lT30 2211 2369 HSCOC4-PEA1 _T31 2211 2369 HSCOC4_PEA_1_T32 2211 2369 HSCOC4_PEA-lT40 2211 2369 Segment cluster HSCOC4_PEA-_1node_39 according to the present invention is 5 supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA-1-TS, HSCOC4_PEA_1_TI 1, HSCOC4_PEA-1_T12, HSCOC4_PEAjl-T14, HSCOC4_PEA_1_TI5, HSCOC4_PEAI-T20, WO 2005/072050 PCT/IB2005/000433 739 HSCOC4_PEA-1-T21, HSCOC4_PEA__T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4-PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 77 below describes the starting and ending position of this segment on each transcript. 5 Table 77 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 2370 2496 HSCOC4_PEA 1 T2 2370 2496 HSCOC4_PEA 1 T3 2370 2496 HSCOC4_PEA 1 T4 2370 2496 HSCOC4_PEA 1-T5 2469 2595 HSCOC4_PEA 1 T7 2167 2293 HSCOC4_PEAIT8 2370 2496 HSCOC4_PEA_1_Ti 1 2370 2496 HSCOC4_PEA_1-T12 2370 2496 HSCOC4_PEA_1_T14 2370 2496 HSCOC4_PEA 1TI5 2370 2496 HSCOC4_PEA_1_T20 2370 2496 HSCOC4_PEA_1_T21 2370 2496 HSCOC4_PEA-lT25 2370 2496 HSCOC4_PEA_1_T28 2370 2496 HSCOC4_PEA_1_T30 2370 2496 HSCOC4_PEA-lT31 2370 2496 HSCOC4_PEAlT32 2370 2496 HSCOC4_PEA_1_T40 2370 2496 Segment cluster HSCOC4_PEA_1_node_43 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 740 segment can be found in the following transcript(s): HSCOC4-PEA-1 T1, HSCOC4-PEA_1_T2, HSCOC4_PEA_1-T3, HSCOC4_PEAAlT4, HSCOC4-PEA_1_T5, HSCOC4_PEA_1-T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEAlT20, 5 HSCOC4_PEAl-T21, HSCOC4_PEA_1_T25, HSCOC4_PEA-lT28, HSCOC4_PEA_1_T30, HSCOC4 PEA_1_T31, HSCOC4_PEA 1_T32 and HSCOC4_PEA_1_T40. Table 78 below describes the starting and ending position of this segment on each transcript. Table 78 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 2572 2769 HSCOC4_PEA-lT2 2572 2769 HSCOC4_PEA_1 T3 2572 2769 HSCOC4_PEA_1_T4 21572 2769 HSCOC4_PEA-lT5 2671 2868 HSCOC4_PEA_T7 2369 2566 HSCOC4_PEA_1_T8 2572 2769 HSCOC4_PEA_1_Ti 1 2572 2769 HSCOC4_PEAI _T12 2572 2769 HSCOC4_PEA_1_T14 2572 2769 HSCOC4-PEA_1_Ti5 2572 2769 HSCOC4_PEA_1_T20 2572 2769 HSCOC4_PEA_1 T21 2572 2769 HSCOC4_PEA_T25 2572 2769 HSCOC4_PEA_1_T28 2572 2769 HSCOC4_PEA_1_T30 2572 2769 HSCOC4-PEAIT31 2572 2769 HSCOC4_PEA_1_T32 2572 2769 WO 2005/072050 PCT/IB2005/000433 741 HSCOC4-PEA-lT40 2572 2769 Segment cluster HSCOC4_PEA_1_node_48 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_T2 and HSCOC4_PEA_1_T3. Table 79 below describes the starting and ending position of this segment on each transcript. Table 79 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T2 2953 3210 HSCOC4_PEA_1_T3 2953 3210 10 Segment cluster HSCOC4_PEA-_node_49 according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA-1_T3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, 15 HSCOC4_PEAI_T7, HSCOC4_PEA_1_T8, HSCOC4_PEAI_T 11, HSCOC4_PEA I_T12, HSCOC4_PEA_1-T14, HSCOC4-PEA-l_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1-T25, HSCOC4_PEA_1_T28, HSCOC4_PEAl-T30, HSCOC4_PEAIT31, HSCOC4_PEAl-T32 and HSCOC4_PEAIT40. Table 80 below describes the starting and ending position of this 20 segment on each transcript. Table 80 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 2953 3092 WO 2005/072050 PCT/IB2005/000433 742 HSCOC4_PEA-lT2 3211 3350 HSCOC4_PEA_1_T3 3211 3350 HSCOC4_PEA_1_T4 2953 3092 HSCOC4_PEA_1_T5 3052 3191 HSCOC4_PEA-T7 2750 2889 HSCOC4_PEA lT8 2953 3092 HSCOC4_PEA_1-Ti 1 2953 3092 HSCOC4_PEA 1 T12 2953 3092 HSCOC4_PEA_1_T14 2953 3092 HSCOC4_PEA 1 Ti5 2953 3092 HSCOC4_PEA_1 T20 2953 3092 HSCOC4_PEA-lT21 2953 3092 HSCOC4_PEAl-T25 2953 3092 HSCOC4_PEAI 1T28 2953 3092 HSCOC4_PEA_1_T30 2953 3092 HSCOC4_PEAI _T31 2953 3092 HSCOC4_PEAIT32 2953 3092 HSCOC4_PEA1 _T40 2953 3092 Segment cluster HSCOC4_PEA_1_node_51 according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_-_Ti, HSCOC4_PEAlT2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4_PEAIT5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_TI 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA-lTi5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEAIT25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31, HSCOC4_PEAIT32 and HSCOC4_PEA_1_T40. Table 81 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 743 Table 81 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_Ti 3206 3415 HSCOC4_PEA_T2 3351 3560 HSCOC4_PEA_1_T3 3464 3673 HSCOC4_PEA_1_T4 3093 3302 HSCOC4_PEA lT5 3192 3401 HSCOC4_PEA_-T7 2890 3099 HSCOC4_PEA_1_T8 3093 3302 HSCOC4_PEA-l_Ti 1 3093 3302 HSCOC4_PEA 1 T12 3093 3302 HSCOC4_PEA-_1T14 3093 3302 HSCOC4_PEA_1_Ti5 3093 3302 HSCOC4_PEAl-T20 3093 3302 HSCOC4_PEA_1_T21 3093 3302 HSCOC4_PEAl-T25 3093 3302 HSCOC4_PEAlT28 3093 3302 HSCOC4_PEAl-T30 3093 3302 HSCOC4_PEA_1_T31 3093 3302 HSCOC4_PEA_1_T32 3093 3302 HSCOC4_PEAl-T40 3093 3302 Segment cluster HSCOC4_PEA_1_node_58 according to the present invention is 5 supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4-PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEAIT3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1-T8, HSCOC4_PEA_1_Tl 1, HSCOC4_PEA-1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEAIT20, WO 2005/072050 PCT/IB2005/000433 744 HSCOC4_PEAlT21, HSCOC4_PEA_1_T25, HSCOC4-PEAIT28, HSCOC4_PEA_1_T30, HSCOC4_PEA_1-T3 1, HSCOC4_PEA_1-T32 and HSCOC4_PEA_1_T40. Table 82 below describes the starting and ending position of this segment on each transcript. 5 Table 82 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_T 3605 3767 HSCOC4_PEA1 _T2 3750 3912 HSCOC4_PEA_1_T3 3863 4025 HSCOC4_PEA_1T4 3492 3654 HSCOC4_PEA_1_T5 3591 3753 HSCOC4_PEA_1_T7 3289 3451 HSCOC4-PEA-1_TS 3492 3654 HSCOC4_PEA l-Ti 1 3492 3654 HSCOC4_PEA_1_T12 3492 3654 HSCOC4_PEA_1_T14 3492 3654 HSCOC4_PEA_1_TI5 3492 3654 HSCOC4_PEAl-T20 3492 3654 HSCOC4_PEA_1_T21 3492 3654 HSCOC4_PEAI T25 3492 3654 HSCOC4_PEA_1T28 3492 3654 HSCOC4_PEA_1_T30 3492 3654 HSCOC4_PEA_1_T31 3492 3654 HSCOC4_PEA__T32 3492 3654 HSCOC4_PEA_1_T40 3492 3654 Segment cluster HSCOC4_PEA_1_node_59 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 745 segment can be found in the following transcript(s): HSCOC4_PEA_1-T4. Table 83 below describes the starting and ending position of this segment on each transcript. Table 83 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T4 3655 3833 5 Segment cluster HSCOC4_PEAInode_62 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_1, HSCOC4-PEA-lT2, HSCOC4_PEA_1T3, HSCOC4_PEA_1 T4, HSCOC4_PEA-lT5, 10 HSCOC4_PEA_1_T7, HSCOC4_PEA_1T8, HSCOC4_PEA_1_11, HSCOC4_PEA_11 12, HSCOC4_PEA-_1T14, HSCOC4_PEA-_1_15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4-PEA_1-T25, HSCOC4-PEA_1_T28, HSCOC4_PEA_1T30, HSCOC4_PEA_1-T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 84 below describes the starting and ending position of this 15 segment on each transcript. Table 84 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 3844 4000 HSCOC4_PEA1 T2 3989 4145 HSCOC4_PEA_1_T3 4102 4258 HSCOC4_PEA lT4 3910 4066 HSCOC4_PEA_1T5 3830 3986 HSCOC4_PEA_1T7 3528 3684 HSCOC4_PEA_1_T8 3731 3887 HSCOC4_PEA_1 T11 3731 3887 WO 2005/072050 PCT/IB2005/000433 746 HSCOC4_PEA 1 T12 3731 3887 HSCOC4_PEA_1 T14 3731 3887 HSCOC4_PEA_-T15 3731 3887 HSCOC4_PEA 1_T20 3731 3887 HSCOC4_PEA_1_T21 3731 3887 HSCOC4_PEA1 1T25 3731 3887 HSCOC4_PEA lT28 3731 3887 HSCOC4_PEA_1_T30 3731 3887 HSCOC4_PEA_1_T31. 3731 3887 HSCOC4_PEA_-T32 3731 3887 HSCOC4_PEA_1_T40 3731 3887 Segment cluster HSCOC4_PEA_1_node_66 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1-Ti, HSCOC4-PEA-lT2, HSCOC4_PEA_1_T3, HSCOC4_PEA-_T4, HSCOC4_PEA_1_T5, HSCOC4_PEAI-T7, HSCOC4_PEA_1_T8, HSCOC4-PEA_1T111, HSCOC4_PEA__T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1-T15, HSCOC4-PEA__T20, HSCOC4_PEA1 T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1-T28, 10 HSCOC4_PEA_1-T30, HSCOC4-PEA-1_T31, HSCOC4_PEA_1_T32 and HSCOC4-PEAIT40. Table 85 below describes the starting and ending position of this segment on each transcript. Table 85 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1T11 4118 4289 HSCOC4_PEA1 T2 4263 4434 HSCOC4_PEA_1_T3 4376 4547 WO 2005/072050 PCT/IB2005/000433 747 HSCOC4_PEA_1-T4 4184 4355 HSCOC4_PEA_1_T5 4104 4275 HSCOC4_PEA_1_T7 3802 3973 HSCOC4-PEA_1_T8 4005 4176 HSCOC4_PEA_1_TIl 4005 4176 HSCOC4_PEA-_1T12 4005 4176 HSCOC4_PEA_1_T14 4005 4176 HSCOC4_PEA_-TI5 4005 4176 HSCOC4_PEA 1_T20 4005 4176 HSCOC4_PEAIT21 4005 4176 HSCOC4_PEA_1 T25 4005 4176 HSCOC4_PEA_1_T28 4005 4176 HSCOC4_PEAlT30 4005 4176 HSCOC4_PEA_lT31 4005 4176 HSCOC4-PEAIT32 4005 4176 HSCOC4_PEA lT40 4005 4176 Segment cluster HSCOC4_PEAInode_72 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA-1_Ti, HSCOC4_PEAl-T2, HSCOC4_PEAlT3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1-T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1-Tll, HSCOC4_PEA-lT12, HSCOC4_PEA_1_T14, HSCOC4_PEA-lT15, HSCOC4_PEA_1_T20, HSCOC4_PEAlT21, HSCOC4_PEA_-lT25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1T30, HSCOC4_PEA-lT31 and HSCOC4_PEA_1_T32. Table 86 below describes the starting and ending position of this segment on each transcript. Table 86 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 748 Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_Ti 4392 4522 HSCOC4_PEA_1 T2 4537 4667 HSCOC4_PEA_1 T3 4650 4780 HSCOC4_PEA 1 T4 4458 4588 HSCOC4_PEA_1 T5 4378 4508 HSCOC4_PEA_1 T7 4076 4206 HSCOC4-PEA__T8 4279 4409 HSCOC4_PEA_1_Ti 1 4279 4409 HSCOC4_PEA_1_T12 4279 4409 HSCOC4-PEA-_1T14 4279 4409 HSCOC4_PEA_1_TI5 4279 4409 HSCOC4_PEA_1-T20 4279 4409 HSCOC4_PEA_1_T21 4279 4409 HSCOC4_PEA-lT25 4279 4409 HSCOC4-PEAIT28 4279 4409 HSCOC4_PEA_1_T30 4279 4409 HSCOC4_PEAl-T31 4279 4409 HSCOC4_PEA_1_T32 4279 4409 Segment cluster HSCOC4_PEA_1_node_77 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_14 and HSCOC4_PEA_1_T20. Table 87 below describes the starting and ending position of this segment on each transcript. Table 87 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 749 Transcript name Segment Segment starting position ending position HSCOC4_PEA1 _T14 4578 4970 HSCOC4_PEA1 _T20 4660 5052 Segment cluster HSCOC4_PEA_1_node_79 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEAl_Ti 1. Table 88 below describes the starting and ending position of this segment on each transcript. Table 88 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_TI1 4638 5686 10 Segment cluster HSCOC4_PEA-_1node_93 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-lT8, HSCOC4_PEA_1_T12 and HSCOC4_PEA_1_T21. Table 89 below describes the starting and ending position of this segment on each transcript. 15 Table 89 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA-_1TS 5085 6566 HSCOC4_PEA I_T12 5289 6770 HSCOC4_PEA_1_T21 5085 6566 WO 2005/072050 PCT/IB2005/000433 750 Segment cluster HSCOC4_PEA_1_node_100 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA__T21. Table 90 below describes the starting and ending position of this segment on each transcript. 5 Table 90 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 T21 6679 6843 Segment cluster HSCOC4_PEAInode_105 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This 10 segment can be found in the following transcript(s): HSCOC4_PEA_1_T28 and HSCOC4_PEAl-T32. Table 91 below describes the starting and ending position of this segment on each transcript. Table 91 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T28 5377 5558 HSCOC4-PEA__T32 5462 5643 15 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (with regard to breast cancer), shown in Table 92. Table 92 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference HSCOC4_0_0_9883 breast malignant tumors BRS 20 WO 2005/072050 PCT/IB2005/000433 751 Segment cluster HSCOC4_PEA_1_node_107 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-l_T25, 5 HSCOC4_PEAlT28 and HSCOC4_PEA-lT32. Table 93 below describes the starting and ending position of this segment on each transcript. Table 93 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T25 5461 5722 HSCOC4_PEA_1_T28 5643 5904 HSCOC4_PEA_1_T32 5728 5989 10 Segment cluster HSCOC4_PEAI-node_108 according to the present invention is supported by 120 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1_T2, HSCOC4_PEA l-T3, HSCOC4_PEA_1_T4, HSCOC4-PEAl-T5, HSCOC4_PEA-lT7, HSCOC4_PEA_1_T8, HSCOC4-PEA-1-Ti 1, HSCOC4_PEAl_T12, 15 HSCOC4-PEAl-T14, HSCOC4-PEA-l_T15, HSCOC4_PEA-lT20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEA-lT30, HSCOC4_PEA_1_T31, HSCOC4_PEA_lT32 and HSCOC4_PEA_1_T40. Table 94 below describes the starting and ending position of this segment on each transcript. 20 Table 94 - Segnent location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1Ti 5574 5706 HSCOC4_PEAI _T2 5719 5851 WO 2005/072050 PCT/IB2005/000433 752 HSCOC4_PEA-1_T3 5832 5964 HSCOC4_PEA_1-T4 5640 5772 HSCOC4_PEA_1 T5 5560 5692 HSCOC4-PEAl-T7 5258 5390 HSCOC4_PEA_1 TS 6952 7084 HSCOC4_PEA 1_Til 6510 6642 HSCOC4_PEAI T12 7156 7288 HSCOC4_PEA 1 T14 5854 5986 HSCOC4_PEA 1 TI5 5414 5546 HSCOC4_PEA_1 T20 5936 6068 HSCOC4_PEA1 1T21 7117 7249 HSCOC4_PEA 1 T25 5723 5855 HSCOC4_PEA_1_T28 5905 6037 HSCOC4_PEA 1 T30 5358 5490 HSCOC4_PEA 1 T31 5546 5678 HSCOC4_PEA 1 T32 5990 6122 HSCOC4_PEA_1_T40 4499 4631 Segment cluster HSCOC4_PEA_1_node_109 according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEAIT25 and HSCOC4_PEA_1_T28. Table 95 below describes the starting and ending position of this segment on each transcript. Table 95 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 T25 5856 5998 HSCOC4_PEA_1_T28 6038 6180 WO 2005/072050 PCT/IB2005/000433 753 Segment cluster HSCOC4_PEA_1_node_110 according to the present invention is supported by 97 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-1_Ti, 5 HSCOC4_PEAl_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEAlT25, HSCOC4_PEA-lT28, HSCOC4_PEA-lT30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and 10 HSCOC4_PEA-1-T40. Table 96 below describes the starting and ending position of this segment on each transcript. Table 96 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 5707 5856 HSCOC4_PEA_ IT2 5852 6001 HSCOC4_PEA 1 T3 5965 6114 HSCOC4_PEA_1_T4 5773 5922 HSCOC4_PEA 1 T5 5693 5842 HSCOC4_PEA 1 T7 5391 5540 HSCOC4_PEA__T8 7085 7234 HSCOC4_PEA 1_11 6643 6792 HSCOC4_PEA_112 7289 7438 HSCOC4_PEA-1._14 5987 6136 HSCOC4_PEA 1 15 5547 5696 HSCOC4_PEA 1 T20 6069 6218 HSCOC4_PEA_1_T21 7250 7399 HSCOC4_PEAlT25 5999 6148 HSCOC4_PEA_lT28 6181 6330 WO 2005/072050 PCT/IB2005/000433 754 HSCOC4_PEAlT30 5491 5640 HSCOC4-PEA_1_T31 5679 5828 HSCOC4_PEA_1 T32 6123 6272 HSCOC4_PEA_1 T40 4632 4781 Segment cluster HSCOC4_PEA_1-node_112 according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1-T11, HSCOC4_PEA_1 T12, HSCOC4_PEA_1_T14, HSCOC4-PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4-PEAl_T21, HSCOC4_PEAIT25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEAl-T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 97 below describes the starting and ending position of this segment on each transcript. Table 97 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 5948 5989 HSCOC4_PEA_1_T2 6093 6134 HSCOC4_PEA 1 T3 6206 6247 HSCOC4_PEA1 1T4 6014 6055 HSCOC4_PEA-1_T5 5934 5975 HSCOC4_PEA 1 T7 5632 5673 HSCOC4_PEAIT8 7326 7367 HSCOC4_PEA 1 T1 6884 6925 HSCOC4_PEA_1_T2 7530 7571 HSCOC4_PEA_1 14 6228 6269 WO 2005/072050 PCT/IB2005/000433 755 HSCOC4_PEAI _TI5 5788 5829 HSCOC4_PEA_1_T20 6310 6351 HSCOC4_PEA_1_T21 7491 7532 HSCOC4-PEA_-T25 6240 6619 HSCOC4_PEA_1_T28 6422 6801 HSCOC4_PEA_1_T30 5732 5773 HSCOC4_PEA_1_T31 5920 5961 HSCOC4_PEA_1_T32 6364 6743 HSCOC4_PEA_1_T40 4873 4914 Segment cluster HSCOC4_PEA_1_node_113 according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA-IT25, HSCOC4_PEA_1_T28 and HSCOC4_PEA_1_T32. Table 98 below describes the starting and ending position of this segment on each transcript. Table 98 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA-lT25 6620 7765 HSCOC4_PEAlT28 6802 7947 HSCOC4_PEA_1_T32 6744 7889 According to an optional embodiment of the present invention, short segments related to 10 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster HSCOC4_PEA-1_node_2 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This 15 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA-lT2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1-T4, HSCOC4_PEA_1_T5, WO 2005/072050 PCT/IB2005/000433 756 HSCOC4_PEA__T7, HSCOC4_PEA_1-T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEAI_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA-lT25, HSCOC4_PEA_1_T28, HSCOC4_PEA _T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and 5 HSCOC4_PEA _T40. Table 99 below describes the starting and ending position of this segment on each transcript. Table 99 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 536 565 HSCOC4_PEA 1 T2 536 565 HSCOC4_PEA_1_T3 536 565 HSCOC4_PEA_1_T4 536 565 HSCOC4_PEA lT5 536 565 HSCOC4_PEA-1-T7 536 565 HSCOC4_PEA I T8 536 565 HSCOC4_PEA 1 Tl 536 565 HSCOC4_PEA_1_T12 536 565 HSCOC4 PEA_1_T14 536 565 HSCOC4_PEA_1_TI5 536 565 HSCOC4_PEA lT20 536 565 HSCOC4_PEA-_-T21 536 565 HSCOC4 PEA_1 T25 536 565 HSCOC4-PEA_1_T28 536 565 HSCOC4_PEA lT30 536 565 HSCOC4_PEAIT31 536 565 HSCOC4_PEA_1_T32 536 565 HSCOC4_PEA-lT40 536 565 WO 2005/072050 PCT/IB2005/000433 757 Segment cluster HSCOC4 PEA _1node_8 according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEAI_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEAAlT3, HSCOC4_PEA_1_T4, HSCOC4-PEA_1-T5, 5 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEAIT14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEAjT30, HSCOC4_PEA-1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA lT40. Table 100 below describes the starting and ending position of this 10 segment on each transcript. Table 100 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 886 966 HSCOC4_PEA_1 T2 886 966 HSCOC4_PEA1 _T3 886 966 HSCOC4_PEA_1_T4 886 966 HSCOC4_PEA1 _T5 886 966 HSCOC4_PEA_1_T7 886 966 HSCOC4_PEA_1_T8 886 966 HSCOC4_PEA_1_TIl 886 966 HSCOC4_PEA_1_T12 886 966 HSCOC4_PEA_T14 886 966 HSCOC4_PEA_T15 886 966 HSCOC4_PEA_1 T20 886 966 HSCOC4_PEA_1_T21 886 966 HSCOC4_PEA_1_T25 886 966 HSCOC4_PEA_1 T28 886 966 HSCOC4_PEA__T30 886 966 WO 2005/072050 PCT/IB2005/000433 758 HSCOC4_PEA I T31 886 966 HSCOC4_PEA_1 T32 886 966 HSCOC4_PEA_1 T40 886 966 Segment cluster HSCOC4_PEA_-node_10 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA-1_T1, HSCOC4_PEA__T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4-PEA-lT5, HSCOC4-PEA_1_T7, HSCOC4_PEA_1_TS, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1-T15, HSCOC4-PEAIT20, HSCOC4_PEA__T21, HSCOC4_PEAl-T25, HSCOC4-PEA_1_T28, 10 HSCOC4_PEA_1T30, HSCOC4_PEAlT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA__T40. Table 101 below describes the starting and ending position of this segment on each transcript. Table 101 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 967 1037 HSCOC4_PEA_1_T2 967 1037 HSCOC4_PEA_1_T3 967 1037 HSCOC4_PEAIT4 967 1037 HSCOC4_PEA._1T5 967 1037 HSCOC4_PEA-_T7 967 1037 HSCOC4_PEA_1_T8 967 1037 HSCOC4_PEA_1_TIl 967 1037 HSCOC4_PEA-1_T12 967 1037 HSCOC4_PEA_1-T14 967 1037 HSCOC4_PEA_1_T15 967 1037 WO 2005/072050 PCT/IB2005/000433 759 HSCOC4_PEA_1T20 967 1037 HSCOC4_PEA_1-T21 967 1037 HSCOC4_PEA 1 T25 967 1037 HSCOC4_PEA__1T28 967 1037 HSCOC4_PEA_1_T30 967 1037 HSCOC4_PEA_1 T31 967 1037 HSCOC4-PEA_1_T32 967 1037 HSCOC4_PEA 1 T40 967 1037 Segment cluster HSCOC4-PEA_1_node_12 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1T3, HSCOC4-PEAl-T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA-LT8, HSCOC4_PEA_1_TI 1, HSCOC4_PEA_1_T12, HSCOC4_PEA-1-T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA-l-T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA-lT30, HSCOC4_PEA_1_T31, HSCOC4-PEA-T32 and HSCOC4_PEA_1_T40. Table 102 below describes the starting and ending position of this segment on each transcript. Table 102 - Segment location on transcripts Trarscript name Segment Segment starting position ending position HSCOC4_PEA 1_TI 1038 1126 HSCOC4_PEA_1_T2 1038 1126 HSCOC4_PEA_1 T3 1038 1126 HSCOC4_PEA_1_T4 1038 1126 HSCOC4_PEA-1_T5 1038 1126 HSCOC4_PEA_1T7 1038 1126 WO 2005/072050 PCT/IB2005/000433 760 HSCOC4_PEA_1-T8 1038 1126 HSCOC4_PEA-_ T11 1038 1126 HSCOC4_PEA_1_T12 1038 1126 HSCOC4-PEA_1_T14 1038 1126 HSCOC4_PEA_1_TI5 1038 1126 HSCOC4_PEA_1_T20 1038 1126 HSCOC4_PEA_1 T21 1038 1126 HSCOC4_PEA_1_T25 1038 1126 HSCOC4_PEA_1 T28 1038 1126 HSCOC4_PEAI 1T30 1038 1126 HSCOC4_PEA_1 T31 1038 1126 HSCOC4_PEA_1_T32 1038 1126 HSCOC4_PEA_1 T40 1038 1126 Segment cluster HSCOC4_PEA_1 node_14 according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4-PEA_1_T2, HSCOC4_PEAl-T3, HSCOC4_PEAIT4, HSCOC4_PEA_1_T5, HSCOC4-PEA_1_T7, HSCOC4_PEA-lT8, HSCOC4_PEA.1_Tl1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1-T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 103 below describes the starting and ending position of this segment on each transcript. Table 103 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 1127 1209 WO 2005/072050 PCT/IB2005/000433 761 HSCOC4_PEA 1 T2 1127 1209 HSCOC4_PEA_1_T3 1127 1209 HSCOC4_PEA 1 T4 1127 1209 HSCOC4_PEA_T5 1127 1209 HSCOC4_PEAIT7 1127 1209 HSCOC4_PEA_T8 1127 1209 HSCOC4_PEA 1_Til 1127 1209 HSCOC4_PEA_1_T12 1127 1209 HSCOC4_PEA_1_T14 1127 1209 HSCOC4_PEA_1-TI5 1127 1209 HSCOC4_PEA_1_T20 1127 1209 HSCOC4_PEA_1_T21 1127 1209 HSCOC4_PEA_1-T25 1127 1209 HSCOC4_PEA_1_T28 1127 1209 HSCOC4_PEA_lT30 1127 1209 HSCOC4_PEAlT31 1127 1209 HSCOC4_PEAl-T32 1127 1209 HSCOC4_PEA_1_T40 1127 1209 Segment cluster HSCOC4_PEA_1_node_17 according to the present invention is. supported by 28 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEAI_Ti, HSCOC4_PEA_1-T2, HSCOC4_PEA_1_T3, HSCOC4-PEAlT4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1T8, HSCOC4_PEA_1T T1, HSCOC4_PEA-1_T12, HSCOC4_PEA_-T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4-PEA_1_T21, HSCOC4_PEA_1T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, 10 HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 104 below describes the starting and ending position of this segment on each transcript. Table 104 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 762 Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 1210 1306 HSCOC4_PEA 1 T2 1210 1306 HSCOC4_PEA 1 T3 1210 1306 HSCOC4_PEA 1 T4 1210 1306 HSCOC4_PEA 1 T5 1210 1306 HSCOC4_PEA1 1T8 1210 1306 HSCOC4_PEA_1-T 1 1210 1306 HSCOC4_PEA 1 12 1210 1306 HSCOC4_PEA_1_T14 1210 1306 HSCOC4_PEA-_1115 1210 1306 HSCOC4_PEA 1 T20 1210 1306 HSCOC4_PEAl-T21 1210 1306 HSCOC4_PEA_1_T25 1210 1306 HSCOC4_PEA-lT28 1210 1306 HSCOC4_PEA_1_T30 1210 1306 HSCOC4_PEA-1-T31 1210 1306 HSCOC4_PEA_1_T32 1210 1306 HSCOC4_PEA_1T40 1210 1306 Segment cluster HSCOC4_PEAInode_19 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4-PEA_1T3, HSCOC4_PEA-lT4, HSCOC4-PEA_1_T5, HSCOC4_PEA-1_T8, HSCOC4_PEA-I_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4-PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA-1_T25, HSCOC4_PEAlT28, HSCOC4_PEA-lT30, WO 2005/072050 PCT/IB2005/000433 763 HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA-lT40. Table 105 below describes the starting and ending position of this segment on each transcript. Table 105 - Segment location on transcripts Transcript name Segment starting position ending position HSCOC4_PEA_1 Ti 1307 1412 HSCOC4_PEA_1 T2 1307 1412 HSCOC4_PEA_1_T3 1307 1412 HSCOC4_PEA_1_T4 1307 1412 HSCOC4_PEA_1_T5 1307 1412 HSCOC4_PEA-1_T8 1307 1412 HSCOC4_PEA_1_Til 1307 1412 HSCOC4_PEA_1_T12 1307 1412 HSCOC4_PEA-1-T14 1307 1412 HSCOC4_PEA_1-TI5 1307 1412 HSCOC4_PEA_T20 1307 1412 HSCOC4_PEAl-T21 1307 1412 HSCOC4_PEA_1T25 1307 1412 HSCOC4_PEA_1T28 1307 1412 HSCOC4_PEA-lT30 1307 1412 HSCOC4_PEA_1_T31 1307 1412 HSCOC4_PEA_1_T32 1307 1412 HSCOC4_PEA-lT40 1307 1412 5 Segment cluster HSCOC4_PEA_1_node_21 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1 _1, HSCOC4_PEA_1T2, HSCOC4-PEA_lT3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1_T5, 10 HSCOC4_PEA-1_T7, HSCOC4_PEA-1-T8, HSCOC4_PEA._1_TI, HSCOC4_PEA_1-T12, WO 2005/072050 PCT/IB2005/000433 764 HSCOC4_PEA_1-T14, HSCOC4-PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T I HSCOC4_PEAlT25, HSCOC4-PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4-PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4-PEA_1_T40. Table 106 below describes the starting and ending position of this 5 segment on each transcript. Table 106 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 1413 1439 HSCOC4_PEAI 1T2 1413 1439 HSCOC4_PEA_1_T3 1413 1439 HSCOC4_PEAIT4 1413 1439 HSCOC4_PEA_1 T5 1413 1439 HSCOC4_PEAl-T7 1210 1236 HSCOC4_PEA-lT8 1413 1439 HSCOC4_PEA_1 TI 1413 1439 HSCOC4_PEA_-T12 1413 1439 HSCOC4_PEA 1_T14 1413 1439 HSCOC4_PEA-I_TI5 1413 1439 HSCOC4_PEA_1_T20 1413 1439 HSCOC4_PEA_1-T21 1413 1439 HSCOC4_PEA_1_T25 1413 1439 HSCOC4_PEA_1_T28 1413 1439 HSCOC4_PEA lT30 1413 1439 HSCOC4_PEA_1_T31 1413 1439 HSCOC4_PEAl-T32 1413 1439 HSCOC4_PEA_1_T40 1413 1439 WO 2005/072050 PCT/IB2005/000433 765 Segment cluster HSCOC4_PEA_1_node_22 according to the present invention is supported by 26 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-l_Ti, HSCOC4_PEA-1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, 5 HSCOC4_PEAlT7, HSCOC4_PEA_1_TS, HSCOC4-PEA_111, HSCOC4_PEA_1_T12, HSCOC4_PEAl-T14, HSCOC4_PEALT15, HSCOC4_PEA__T20, HSCOC4_PEA_1_T21, HSCOC4_PEAlT25, HSCOC4_PEA_1_T28, HSCOC4-PEA_1-T30, HSCOC4PEAAlT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 107 below describes the starting and ending position of this 10 segment on each transcript. Table 107 - Segment location on transcripts Transcript name Segment Segment starting position, ending position HSCOC4_PEA_1 Tl 1440 1545 HSCOC4_PEA_1_T2 1440 1545 HSCOC4-PEA_1_T3 1440 1545 HSCOC4_PEA-lT4 1440 1545 HSCOC4-PEAl-T5 1440 1545 HSCOC4-PEA_-T7 1237 1342 HSCOC4_PEA_ iT8 1440 1545 HSCOC4_PEA_1_TI1 1440 1545 HSCOC4_PEA-1_T12 1440 1545 HSCOC4_PEAI_T14 1440 1545 HSCOC4_PEA_1_TI5 1440 1545 HSCOC4_PEA_1_T20 1440 1545 HSCOC4_PEA_1_T21 1440 1545 HSCOC4_PEA_ IT25 1440 1545 HSCOC4-PEA_1_T28 1440 1545 HSCOC4_PEA_1 T30 1440 1545 WO 2005/072050 PCT/IB2005/000433 766 HSCOC4_PEA_1_T31 1440 1545 HSCOC4_PEA_1_T32 1440 1545 HSCOC4_PEAIT40 1440 1545 Segment cluster HSCOC4_PEA_1_node_28 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1-Ti, HSCOC4_PEAlT2, HSCOC4_PEA_1_T3, HSCOC4_PEA-1_T4, HSCOC4_PEA_1_T5, HSCOC4-PEA_1_T7, HSCOC4_PEA-lT8, HSCOC4PEAI._TIl, HSCOC4_PEA-1_T12, HSCOC4_PEA-1_T14, HSCOC4PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA-lT30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 108 below describes the starting and ending position of this segment on each transcript. Table 108 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4 PEA_1_TI 1546 1661 HSCOC4_PEA_1_T2 1546 1661 HSCOC4 PEA_T3 1546 1661 HSCOC4_PEA_T4 1546 1661 HSCOC4_PEA_T5 1546 1661 HSCOC4_PEAIT7 1343 1458 HSCOC4_PEA-lT8 1546 1661 HSCOC4_PEA_1_TIl 1546 1661 HSCOC4_PEA-1_T12 1546 1661 HSCOC4_PEA_1_T14 1546 1661 HSCOC4_PEA_1_TI5 1546 1661 WO 2005/072050 PCT/IB2005/000433 767 HSCOC4_PEA_-T20 1546 1661 HSCOC4_PEA_1_T21 1546 1661 HSCOC4_PEAI 1T25 1546 1661 HSCOC4_PEA 1 T28 1546 1661 HSCOC4_PEA_1_T30 1546 1661 HSCOC4-PEAIT31 1546 1661 HSCOC4_PEA1 1T32 1546 1661 HSCOC4_PEAlT40 1546 1661 Segment cluster HSCOC4_PEA_1_node_29 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4-PEA_1_T5. Table 109 below describes the starting and ending position of this segment on each transcript. Table 109 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEAl-T5 1662 1760 10 Segment cluster HSCOC4_PEA-_node_41 according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4-PEAI_TI, HSCOC4_PEA_1_T2, HSCOC4_PEA-1_T3, HSCOC4-PEA_1T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEAl-T8, HSCOC4_PEA-lT11, HSCOC4_PEA_1_12, 15 HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA-1-T21, HSCOC4_PEA_1T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1T30, HSCOC4_PEAlT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 110 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 768 Table 110 - Segment location on transcripts Transcript name Segment Seent starting position ending position HSCOC4-PEA_Ti 2497 2571 HSCOC4_PEA I T2 2497 2571 HSCOC4_PEA 1T3 2497 2571 HSCOC4_PEA _T4 2497 2571 HSCOC4_PEA 1_T5 2596 2670 HSCOC4_PEA 1 T7 2294 2368 HSCOC4_PEA_1 T8 2497 2571 HSCOC4_PEA1-Ti1 2497 2571 HSCOC4_PEA 1 T12 2497 2571 HSCOC4_PEA_1 14 2497 2571 HSCOC4_PEA_1-T15 2497 2571 HSCOC4_PEA 1 T20 2497 2571 HSCOC4_PEA 1T21 2497 2571 HSCOC4_PEA_1 T25 2497 2571 HSCOC4_PEA__T28 2497 2571 HSCOC4_PEA_1_T30 2497 2571 HSCOC4_PEA_1-T31 2497 2571 HSCOC4_PEA_1_T32 2497 2571 HSCOC4_PEA_1_T40 2497 2571 Segment cluster HSCOC4-PEA_1_node_45 according to the present invention is 5 supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4-PEA_1_T2, HSCOC4_PEA_lT3, HSCOC4-PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA-lT7, HSCOC4-PEA_1T8, HSCOC4_PEA-1._T11, HSCOC4_PEA_1_12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1_T20, WO 2005/072050 PCT/IB2005/000433 76 9 HSCOC4_PEA_1_T21, HSCOC4_PEAlT25, HSCOC4_PEAlT28, HSCOC4_PEA_1_T30, HSCOC4_PEAlT31, HSCOC4_PEA__T32 and HSCOC4_PEA_1_T40. Table 111 below describes the starting and ending position of this segment on each transcript. 5 Table 111 - Segment location on transcripts Transcript nam e Segment Segment starting position ending position HSCOC4_PEA_lTi 2770 2881 HSCOC4_PEA_1T2 2770 2881 HSCOC4_PEA-lT3 2770 2881 HSCOC4_PEA-l_ 4 2770 2881 HSCOC4_PEAlT5 2869 2980 HSCOC4_PEA-1_T7 2567 2678 HSCOC4_PEA_1T8 2770 2881 HSCOC4-PEA-lT11 2770 2881 HSCOC4_PEA__12 2770 2881 HSCOC4_PEA_1_114 2770 2881 HSCOC4_PEA_1_15 2770 2881 HSCOC4-PEA_1_T20 2770 2881 HSCOC4_PEA_1T21 2770 2881 HSCOC4_PEA_1_T25 2770 2881 HSCOC4_PEAlT28 2770 2881 HSCOC4_PEA-lT30 2770 2881 HSCOC4_PEA_1_T31 2770 2881 HSCOC4_PEA_1_T32 2770 2881 HSCOC4_PEA_1_T40 2770 2881 Segment cluster HSCOC4_PEA_1_node_47 according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 770 segment can be found in the following transcript(s): HSCOC4-PEA_1-T1, HSCOC4_PEA_1_T2, HSCOC4_PEA-lT3, HSCOC4_PEAlT4, HSCOC4_PEAIT5, HSCOC4_PEA-lT7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_TIl, HSCOC4-PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA-1_T20, 5 HSCOC4_PEAl-T21, HSCOC4_PEA_1_T25, HSCOC4_PEAIT28, HSCOC4_PEA-lT30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 112 below describes the starting and ending position of this segment on each transcript. Table 112 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA1 _Ti 2882 2952 HSCOC4_PEA_1_T2 2882 2952 HSCOC4_PEA1 _T3 2882 2952 HSCOC4-PEA_1T4 2882 2952 HSCOC4_PEA_1_T5 2981 3051 HSCOC4_PEA_1T7 2679 2749 HSCOC4_PEA_1T8 2882 2952 HSCOC4_PEA_1_T11 2882 2952 HSCOC4_PEA-1_T12 2882 2952 HSCOC4_PEA_1_14 2882 2952 HSCOC4_PEA_1_15 2882 2952 HSCOC4_PEA_1_T20 2882 2952 HSCOC4_PEA-1_T21 2882 2952 HSCOC4_PEA_1-T25 2882 2952 HSCOC4_PEA_1T28 2882 2952 HSCOC4-PEA_1_T30 2882 2952 HSCOC4_PEA_1_T31 2882 2952 HSCOC4_PEA_1_T32 2882 2952 WO 2005/072050 PCT/IB2005/000433 771 HSCOC4_PEAI 1T40 2882 2952 Segment cluster HSCOC4_PEA_1_node_50 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti and HSCOC4_PEA_1_T3. Table 113 below describes the starting and ending position of this segment on each transcript. Table 113 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 3093 3205 HSCOC4_PEA-1-T3 3351 3463 10 Segment cluster HSCOC4_PEA_1_node_53 according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEAIT3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, 15 HSCOC4_PEAIT7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Til , HSCOC4_PEA-1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEAlT20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4_PEAIT31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 114 below describes the starting and ending position of this 20 segment on each transcript. Table 114 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 3416 3467 WO 2005/072050 PCT/IB2005/000433 772 HSCOC4_PEA 1_T2 3561 3612 HSCOC4_PEA_1_T3 3674 3725 HSCOC4_PEAI T4 3303 3354 HSCOC4_PEA_1_T5 3402 3453 HSCOC4_PEA_1_T7 3100 3151 HSCOC4_PEA_1_T8 3303 3354 HSCOC4_PEA_1_T 11 3303 3354 HSCOC4_PEA_1-T12 3303 3354 HSCOC4_PEA_1-T14 3303 3354 HSCOC4_PEA_1_TI5 3303 3354 HSCOC4_PEA -T20 3303 3354 HSCOC4-PEA 1_T21 3303 3354 HSCOC4_PEA_1_T25 3303 3354 HSCOC4-PEA_1_T28 3303 3354 HSCOC4_PEA-lT30 3303 3354 HSCOC4_PEA_1_T31 3303 3354 HSCOC4_PEA_1_T32 3303 3354 HSCOC4_PEA_1_T40 3303 3354 Segment cluster HSCOC4_PEA-_1node_55 according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1_T2, HSCOC4_PEAAlT3, HSCOC4_PEAAlT4, HSCOC4_PEA_1_T5, HSCOC4-PEA_1_T7, HSCOC4_PEAl_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 115 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 773 Table 115 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1 Ti 3468 3557 HSCOC4_PEA_1_T2 3613 3702 HSCOC4_PEA lT3 3726 3815 HSCOC4_PEA__T4 3355 3444 HSCOC4_PEA1 _T5 3454 3543 HSCOC4_PEA lT7 3152 3241 HSCOC4_PEA__T8 3355 3444 HSCOC4_PEA_1_Til 3355 3444 HSCOC4_PEA__1T12 3355 3444 HSCOC4_PEA_1_T14 3355 3444 HSCOC4_PEA_1_T15 3355 3444 HSCOC4_PEA_1 T20 3355 3444 HSCOC4_PEA_1 T21 3355 3444 HSCOC4_PEA_1_T25 3355 3444 HSCOC4_PEAI_T28 3355 3444 HSCOC4_PEA-lT30 3355 3444 HSCOC4_PEA_1_T31 3355 3444 HSCOC4_PEA_1_T32 3355 3444 HSCOC4_PEA_1_T40 3355 3444 Segment cluster HSCOC4_PEA_1_node_57 according to the present invention is 5 supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEAlT2, HSCOC4_PEA-lT3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4-PEA_1_T8, HSCOC4_PEA-_1T1, HSCOC4-PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4-PEA_1_15, HSCOC4_PEA_1_T20, WO 2005/072050 PCT/IB2005/000433 774 HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEAIT30, HSCOC4_PEA-T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 116 below describes the starting and ending position of this segment on each transcript. 5 Table 116 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 3558 3604 HSCOC4_PEA_1_T2 3703 3749 HSCOC4_PEA_1_T3 3816 3862 HSCOC4_PEA_1_T4 3445 3491 HSCOC4-PEA_1 T5 3544 3590 HSCOC4_PEA_1_T7 3242 3288 HSCOC4_PEA_1_T8 3445 3491 HSCOC4_PEA1 _T 11 3445 3491 HSCOC4_PEA_1_T12 3445 3491 HSCOC4_PEA_1_T14 3445 3491 HSCOC4_PEA_1_Ti5 3445 3491 HSCOC4_PEA1 _T20 3445 3491 HSCOC4_PEA_1_T21 3445 3491 HSCOC4_PEA__T25 3445 3491 HSCOC4_PEA lT28 3445 3491 HSCOC4_PEA1 _T30 3445 3491 HSCOC4_PEA_1-T31 3445 3491 HSCOC4_PEAlT32 3445 3491 HSCOC4_PEA_1_T40 3445 3491 Segment cluster HSCOC4_PEA_1-node_60 according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 775 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEAIT3, HSCOC4_PEA__T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA _T8, HSCOC4_PEA_1_11, HSCOC4_PEA_1_T12, HSCOC4 PEA_1-T14, HSCOC4_PEA_1-TI5, HSCOC4_PEA_ IT20, 5 HSCOC4PEAAlT21, HSCOC4-PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEAlT30, HSCOC4_PEA_1_T31, HSCOC4_PEAIT32 and HSCOC4_PEA-lT40. Table 117 below describes the starting and ending position of this segment on each transcript. Table 117 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 3768 3843 HSCOC4_PEA 1 T2 3913 3988 HSCOC4_PEA IT3 4026 4101 HSCOC4_PEA 1 T4 3834 3909 HSCOC4_PEA 1 T5 3754 3829 HSCOC4_PEA 1 T7 3452 3527 HSCOC4-PEA 1_TS 3655 3730 HSCOC4-PEA_1_T 1 3655 3730 HSCOC4_PEA_112 3655 3730 HSCOC4_PEA_1_T14 3655 3730 HSCOC4_PEA 1 15 3655 3730 HSCOC4_PEA1 1T20 3655 3730 HSCOC4_PEA_1_T21 3655 3730 HSCOC4_PEA 1 T25 3655 3730 HSCOC4_PEA1 1T28 3655 3730 HSCOC4_PEA1 T30 3655 3730 HSCOC4_PEA__T31 3655 3730 HSCOC4_PEA_1_T32 3655 3730 WO 2005/072050 PCT/IB2005/000433 776 HSCOC4_PEAlT40 3655 3730 Segment cluster HSCOC4_PEA-_node_64 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4-PEA_1T5, 5 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4-PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4-PEA_1_T30, HSCOC4_PEA_1_T31, HSCOC4_PEAIT32 and HSCOC4_PEA_1_T40. Table 118 below describes the starting and ending position of this 10 segment on each transcript. Table 118 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 4001 4117 HSCOC4_PEA 1 T2 4146 4262 HSCOC4_PEA_1 T3 4259 4375 HSCOC4_PEA_1 T4 4067 4183 HSCOC4_PEA 1 T5 3987 4103 HSCOC4_PEA 1 T7 3685 3801 HSCOC4_PEA_1_T8 3888 4004 HSCOC4_PEA_1ITIl 3888 4004 HSCOC4_PEA 1_T12 3888 4004 HSCOC4_PEA_1_T14 3888 4004 HSCOC4_PEA_1ITI5 3888 4004 HSCOC4_PEA_1_T20 3888 4004 HSCOC4_PEA 1 T21 3888 4004 HSCOC4_PEA_1-T25 3888 4004 HSCOC4_PEA_1 T28 3888 4004 WO 2005/072050 PCT/IB2005/000433 777 HSCOC4_PEA_1_T30 3888 4004 HSCOC4_PEA-1_T31 3888 4004 HSCOC4_PEA_1_T32 3888 4004 HSCOC4_PEAlT40 3888 4004 Segment cluster HSCOC4_PEA_1_node_69 according to the present invention can be found in the following transcript(s): HSCOC4-PEA_1_TI, HSCOC4_PEA_1_T2, 5 HSCOC4-PEAl T3, HSCOC4_PEA-1_T4, HSCOC4_PEAJlT5, HSCOC4_PEA_1-T7, HSCOC4_PEA_1_T8, HSCOC4-PEA_1J 11, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_-lT20, HSCOC4_PEA_1-T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4-PEA_1_T3 1, HSCOC4_PEA_1_T32 and HSCOC4_PEAl-T40. Table 119 below 10 describes the starting and ending position of this segment, on each transcript. Table 119 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_TI 4290 4309 HSCOC4_PEA_1 T2 4435 4454 HSCOC4-PEA_1_T3 4548 4567 HSCOC4_PEA_1_T4 4356 4375 HSCOC4_PEA_1_T5 4276 4295 HSCOC4_PEAI _T7 3974 3993 HSCOC4_PEA_1_T8 4177 4196 HSCOC4_PEA_1_TI1 4177 4196 HSCOC4_PEA_1_T12 4177 4196 HSCOC4_PEAl_T14 4177 4196 HSCOC4_PEA_1_TI5 4177 4196 HSCOC4_PEA_1_T20 4177 4196 WO 2005/072050 PCT/IB2005/000433 778 HSCOC4_PEAI T21 4177 4196 HSCOC4_PEAl-T25 4177 4196 HSCOC4_PEA I T28 4177 4196 HSCOC4 PEAI T30 4177 4196 HSCOC4_PEAI 1T31 4177 4196 HSCOC4_PEA_1_T32 4177 4196 HSCOC4_PEA__T40 4177 4196 Segment cluster HSCOC4_PEA_1_node_70 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1 T2, HSCOC4_PEAJT3, HSCOC4_PEA-lT4, HSCOC4_PEAIT5, HSCOC4_PEA_1_T7, HSCOC4-PEA-1_TS, HSCOC4_PEA_1_TIl , HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA-lT20, HSCOC4_PEA-lT21, HSCOC4_PEA__T25, HSCOC4-PEAl-T28, 10 HSCOC4-PEA_1_T30, HSCOC4-PEA_1_T31 and HSCOC4_PEAIT32. Table 120 below describes the starting and ending position of this segment on each transcript. Table 120 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_TI 4310 4349 HSCOC4_PEA_T2 4455 4494 HSCOC4_PEA_1_T3 4568 4607 HSCOC4_PEA_1_T4 4376 4415 HSCOC4_PEA_1_T5 4296 4335 HSCOC4_PEA_1_T7 3994 4033 HSCOC4_PEA_1_T8 4197 4236 HSCOC4_PEA_1_TIl 4197 4236 WO 2005/072050 PCT/IB2005/000433 779 HSCOC4_PEA_1 T12 4197 4236 HSCOC4_PEA_1 T14 4197 4236 HSCOC4_PEA 1 TI5 4197 4236 HSCOC4_PEA_1_T20 4197 4236 HSCOC4-PEA-l_T21 4197 4236 HSCOC4_PEAI 1T25 4197 4236 HSCOC4-PEA-lT28 4197 4236 HSCOC4_PEA_1_T30 4197 4236 HSCOC4_PEA_1_T31 4197 4236 HSCOC4_PEA-lT32 4197 4236 Segment cluster HSCOC4-PEA-_node_71 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4-PEA_1_T2, HSCOC4_PEA-l-T3, HSCOC4_PEA__T4, HSCOC4_PEAl-T5, HSCOC4_PEA__T7, HSCOC4_PEA-lTS, HSCOC4-PEA_1_Tl1, HSCOC4_PEA_1_12, HSCOC4-PEA1 1T14, HSCOC4_PEA_1_15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA-lT28, 10 HSCOC4_PEA_1_T30, HSCOC4-PEA__T31 and HSCOC4_PEA_1_T32. Table 121 below describes the starting and ending position of this segment on each transcript. Table 121 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 TI 4350 4391 HSCOC4_PEA 1T2 4495 4536 HSCOC4_PEA_1 T3 4608 4649 HSCOC4_PEA_1_T4 4416 4457 HSCOC4_PEA_1_T5 4336 4377 WO 2005/072050 PCT/IB2005/000433 780 HSCOC4_PEA_1 T7 4034 4075 HSCOC4_PEA 1_T8 4237 4278 HSCOC4_PEA-l_ 11 4237 4278 HSCOC4_PEA _1T12 4237 4278 HSCOC4_PEA_1_T14 4237 4278 HSCOC4-PEA_1_TI5 4237 4278 HSCOC4_PEA_1_T20 4237 4278 HSCOC4_PEA_1_T21 4237 4278 HSCOC4_PEA_1_T25 4237 4278 HSCOC4_PEA_1-T28 4237 4278 HSCOC4_PEA_1T30 4237 4278 HSCOC4_PEA_1_T31 4237 4278 HSCOC4_PEA_1_T32 4237 4278 Segment cluster HSCOC4-PEA_1_node_73 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_T20. Table 122 below describes the starting and ending position of this segment on each transcript. Table 122 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T20 4410 4491 10 Segment cluster HSCOC4_PEA_1_node_74 according to the present invention can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1_T2, HSCOC4_PEA_1T3, HSCOC4-PEA_1_T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1T7, HSCOC4_PEAl-T8, HSCOC4_PEAT 11, HSCOC4_PEA_1_112, HSCOC4-PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4-PEA_1_T20, HSCOC4-PEA_1_T21, WO 2005/072050 PCT/IB2005/000433 781 HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA-lT32. Table 123 below describes the starting and ending position of this segment on each transcript Table 123 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_Ti 4523 4546 HSCOC4_PEA_1_T2 4668 4691 HSCOC4_PEA_1 T3 4781 4804 HSCOC4_PEA1 _T4 4589 4612 HSCOC4_PEA1 _T5 4509 4532 HSCOC4_PEA_1T7 4207 4230 HSCOC4_PEA_1 T8 4410 4433 HSCOC4-PEA_1_Tll 4410 4433 HSCOC4_PEA1 _T12 4410 4433 HSCOC4_PEA_1_T14 4410 4433 HSCOC4_PEA_1_TI5 4410 4433 HSCOC4_PEA_1_T20 4492 4515 HSCOC4-PEA1 _T21 4410 4433 HSCOC4_PEA__T25 4410 4433 HSCOC4_PEAI _T28 4410 4433 HSCOC4_PEA_1_T30 4410 4433 HSCOC4-PEA__T31 4410 4433 HSCOC4_PEA__T32 4410 4433 5 Segment cluster HSCOC4_PEA_1_node_75 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4PEA_1_TI, 10 HSCOC4_PEAJlT2, HSCOC4_PEAAlT3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1_T5, WO 2005/072050 PCT/IB2005/000433 782 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA-1_TI , HSCOC4_PEAl_T12, HSCOC4_PEA_1_T14, HSCOC4_PEAT15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA-lT25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA-lT32. Table 124 below 5 describes the starting and ending position of this segment on each transcript. Table 124 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA _1T1 4547 4626 HSCOC4_PEA_1_T2 4692 4771 HSCOC4_PEA 1_T3 4805 4884 HSCOC4_PEA_1T4 4613 4692 HSCOC4_PEA_1_T5 4533 4612 HSCOC4_PEA_1_T7 4231 4310 HSCOC4_PEA_1_T8 4434 4513 HSCOC4_PEAl-Tll 4434 4513 HSCOC4_PEA_1_12 4434 4513 HSCOC4_PEA1114 4434 4513 HSCOC4_PEA_1_15 4434 4513 HSCOC4_PEA_1T20 4516 4595 HSCOC4_PEA-lT21 4434 4513 HSCOC4_PEA_1T25 4434 4513 HSCOC4_PEA_1T28 4434 4513 HSCOC4_PEA1_T30 4434 4513 HSCOC4_PEA_1_131 4434 4513 HSCOC4-PEA_1_T32 4434 4513 Segment cluster HSCOC4_PEA_1_node-76 according to the present invention is 10 supported by 66 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 783 segment can be found in the fJllowing transcript(s): HSCOC4_PEA_1-T1, HSCOC4_PEA_-T2, HSCOC4_PEA_1_T3, HSCOC4_PEA 1_T4, HSCOC4_PEA_1_T5, HSCOC4_PEAlT7, HSCOC4_PEA-1-T8, HSCOC4_PEA_1_Tll, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1 TI5, HSCOC4_PEA__T20, 5 HSCOC4_PEA_1_T21, HSCOC4_PEAIT25, HSCOC4_PEAIT28, HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 125 below describes the starting and ending position of this segment on each transcript. Table 125 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 4627 4690 HSCOC4_PEA1 _T2 4772 4835 HSCOC4_PEAIT3 4885 4948 HSCOC4_PEA_1_T4 4693 4756 HSCOC4_PEA_-T5 4613 4676 HSCOC4_PEA1 _T7 4311 4374 HSCOC4_PEA_1_T8 4514 4577 HSCOC4_PEA_1 TI 4514 4577 HSCOC4_PEA_1-T12 4514 4577 HSCOC4_PEAI _T14 4514 4577 HSCOC4_PEA_1_TI5 4514 4577 HSCOC4_PEA_1_T20 4596 4659 HSCOC4_PEA_1_T21 4514 4577 HSCOC4_PEA-_T25 4514 4577 HSCOC4-PEA_1_T28 4514 4577 HSCOC4_PEA_1_T30 4514 4577 HSCOC4_PEA_1_T31 4514 4577 HSCOC4_PEA-_1T32 4514 4577 10 WO 2005/072050 PCT/IB2005/000433 784 Segment cluster HSCOC4_PEAInode_78 according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_1-Ti, HSCOC4_PEA_1_T2, HSCOC4-PEA_1_T3, HSCOC4_PEA-1_T4, HSCOC4_PEA_1-T5, 5 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA.1_T 11, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA-lT28, HSCOC4-PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 126 below describes the starting and ending position of this segment on each transcript. 10 Table 126 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA 1_TI 4691 4750 HSCOC4_PEA_1_T2 4836 4895 HSCOC4_PEA 1T3 4949 5008 HSCOC4_PEA_1_T4 4757 4816 HSCOC4_PEA 1_T5 4677 4736 HSCOC4_PEAl-T7 4375 4434 HSCOC4_PEA_1_T8 4578 4637 HSCOC4_PEA_1_T 1 4578 4637 HSCOC4_PEA_1_12 4578 4637 HSCOC4_PEA_1_T14 4971 5030 HSCOC4_PEA_1_15 4578 4637 HSCOC4_PEA_1_T20 5053 5112 HSCOC4_PEA_1_T21 4578 4637 HSCOC4_PEA_1_T25 4578 4637 HSCOC4_PEA_1_T28 4578 4637 HSCOC4_PEA_1T30 4578 4637 HSCOC4_PEA_1T31 4578 4637 WO 2005/072050 PCT/IB2005/000433 785 HSCOC4_PEA_1_T32 4578 4637 Segment cluster HSCOC4_PEA_1_node_80 according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1-T1, HSCOC4_PEA_-lT2, HSCOC4_PEA_1_T3, HSCOC4_PEA-lT4, HSCOC4_PEAlT5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEAl_Ti 1, HSCOC4_PEA-I_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA-1-T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEAlT30, HSCOC4_PEA_1_T31 and HSCOC4_PEA lT32. Table 127 below describes the starting and ending position of this segment on each transcript. Table 127 - Segment location on transcripts Transcript name. Segment Segment starting position ending position HSCOC4_PEA_ 1_TI 4751 4844 HSCOC4_PEA_1_T2 4896 4989 HSCOC4_PEA1 _T3 5009 5102 HSCOC4_PEA1 T4 4817 4910 HSCOC4_PEA_1-T5 4737 4830 HSCOC4_PEA_1_T7 4435 4528 HSCOC4_PEA_lT8 4638 4731 HSCOC4_PEAl_T1 5687 5780 HSCOC4_PEA_1_112 4638 4731 HSCOC4_PEA_1-T14 5031 5124 HSCOC4-PEA_1_15 4638 4731 HSCOC4_PEA_1T20 5113 5206 HSCOC4_PEA_1-T21 4638 4731 HSCOC4_PEA-lT25 4638 4731 WO 2005/072050 PCT/IB2005/000433 786 HSCOC4_PEA_1-T28 4638 4731 HSCOC4_PEA_1_T30 4638 4731 HSCOC4_PEA__T31 4638 4731 HSCOC4_PEA_1 T32 4638 4731 Segment cluster HSCOC4-PEA_1_node_82 according to the present invention can be found in the following transcript(s): HSCOC4-PEA-IT1, HSCOC4_PEA_1_T2, 5 HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4_PEAl-T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_ _T8, HSCOC4_PEA1-TIl1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1-T15, HSCOC4_PEA-lT20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4_PEA _T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 128 below describes the starting and 10 ending position of this segment on each transcript. Table 128 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA l_Ti 4845 4855 HSCOC4_PEA_1_T2 4990 5000 HSCOC4_PEAl_T3 5103 5113 HSCOC4_PEA_l_T4 4911 4921 HSCOC4_PEA_1_T5 4831 4841 HSCOC4_PEA _1T7 4529 4539 HSCOC4_PEA_1_T8 4732 4742 HSCOC4_PEA_1_Ti1 5781 5791 HSCOC4_PEA_1_T12 4732 4742 HSCOC4_PEA_1_T14 5125 5135 HSCOC4_PEA_1_TI5 4732 4742 HSCOC4-PEA_1_T20 5207 5217 WO 2005/072050 PCT/IB2005/000433 787 HSCOC4-PEA_1_T21 4732 4742 HSCOC4_PEA_1_T25 4732 4742 HSCOC4_PEA-lT28 4732 4742 HSCOC4_PEA_1_T30 4732 4742 HSCOC4_PEA_1_T31 4732 4742 HSCOC4_PEA_1_T32 4732 4742 Segment cluster HSCOC4_PEA_1-node_83 according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4-PEA-lT5, HSCOC4_PEA1 1T7, HSCOC4_PEA-lT8, HSCOC4_PEA_1_11, HSCOC4_PEA_1_T12, HSCOC4_PEA_1 T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1T21, HSCOC4_PEA-lT25, HSCOC4_PEA-lT28, 10 HSCOC4_PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 129 below describes the starting and ending position of this segment on each transcript. Table 129 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA _1T1 4856 4971 HSCOC4_PEA1 T2 5001 5116 HSCOC4_PEA_1_T3 5114 5229 HSCOC4_PEA__T4 4922 5037 HSCOC4_PEA_1_T5 4842 4957 HSCOC4_PEA1 T7 4540 4655 HSCOC4_PEA_1_18 4743 4858 HSCOC4_PEA_1_T1l 5792 5907 HSCOC4_PEA_1_T12 4743 4858 WO 2005/072050 PCT/IB2005/000433 788 HSCOC4_PEA 1_T14 5136 5251 HSCOC4_PEA-_1TI5 4743 4858 HSCOC4_PEA_1_T20 5218 5333 HSCOC4_PEA_1_T21 4743 4858 HSCOC4_PEA-lT25 4743 4858 HSCOC4_PEAlT28 4743 4858 HSCOC4_PEA_1_T30 4743 4858 HSCOC4_PEA_1_T31 4743 4858 HSCOC4_PEA_1_T32 4743 4858 Segment cluster HSCOC4_PEA_1_node_84 according to the present invention can be found in the following transcript(s): HSCOC4_PEAl_Tl, HSCOC4_PEA_1_T2, 5 HSCOC4_PEA-lT3, HSCOC4_PEA-lT4, HSCOC4_PEA-l-T5, HSCOC4_PEAlT7, HSCOC4_PEAL-TS, HSCOC4_PEA_1-T 1, HSCOC4_PEA_1_12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1 T20, HSCOC4_PEA_1_T21, HSCOC4_PEAlT25, HSCOC4_PEA_1_T28, HSCOC4_PEA__T30, HSCOC4-PEA-lT31 and HSCOC4-PEA-lT32. Table 130 below describes the starting and 10 ending position of this segment on each transcript. Table 130 - Segnent location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA _1T1 4972 4984 HSCOC4_PEA_1 T2 5117 5129 HSCOC4_PEA_1 T3 5230 5242 HSCOC4_PEA_1_T4 5038 5050 HSCOC4_PEA_1_T5 4958 4970 HSCOC4-PEA_1_T7 4656 4668 HSCOC4_PEA_1_T8 4859 4871 WO 2005/072050 PCT/IB2005/000433 789 HSCOC4_PEA-1_TI1 5908 5920 HSCOC4-PEA_1_T12 4859 4871 HSCOC4_PEA_1_T14 5252 5264 HSCOC4_PEA_1_T15 4859 4871 HSCOC4-PEA_1_T20 5334 5346 HSCOC4_PEA_1-T21 4859 4871 HSCOC4-PEA-1_T25 4859 4871 HSCOC4_PEA_-T28 4859 4871 HSCOC4_PEAlT30 4859 4871 HSCOC4_PEA_1_T31 4859 4871 HSCOC4-PEA-lT32 4859 4871 Segment cluster HSCOC4_PEA_1_node_85 according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4-PEA_1_TI, HSCOC4_PEAl-T2, HSCOC4PEA_1_T3, HSCOC4_PEA_1-T4, HSCOC4_PEA-l_T5, HSCOC4-PEA_1_T7, HSCOC4_PEA-lT8, HSCOC4_PEA-1_TI 1, HSCOC4_PEA-1_T12, HSCOC4_PEA-_1914, HSCOC4_PEA-lT20, HSCOC4-PEA_1_T21, HSCOC4_PEA9l-T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T30, 10 HSCOC4_PEA_1_T31 and HSCOC4_PEA-lT32. Table 131 below describes the starting and ending position of this segment on each transcript. Table 131 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 4985 5031 HSCOC4_PEA1 _T2 5130 5176 HSCOC4_PEA_1_T3 5243 5289 HSCOC4_PEA_1_T4 5051 5097 WO 2005/072050 PCT/IB2005/000433 790 HSCOC4_PEA 1 T5 4971 5017 HSCOC4_PEA_1 T7 4669 4715 HSCOC4_PEA_1_T8 4872 4918 HSCOC4_PEA 1_Tll 5921 5967 HSCOC4_PEA_1_T12 4872 4918 HSCOC4_PEA_1-T14 5265 5311 HSCOC4_PEA_1_T20 5347 5393 HSCOC4_PEA_1_T21 4872 4918 HSCOC4_PEA_1_T25 4872 4918 HSCOC4_PEA__T28 4872 4918 HSCOC4_PEA_1_T30 4872 4918 HSCOC4_PEA_1_T31 4872 4918 HSCOC4_PEA_1_T32 4872 4918 Segment cluster HSCOC4_PEA_1_node-86 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_T12. Table 132 below describes the starting and ending position of this segment on each transcript. Table 132 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEAT112 4919 5032 10 Segment cluster HSCOC4_PEA_1_node_87 according to the present invention is supported by 74 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA_LT1, HSCOC4_PEA_1_T2, HSCOC4_PEA_1T3, HSCOC4_PEAlT4, HSCOC4_PEA_1_T5, HSCOC4_PEA-lT7, HSCOC4_PEA-1_T8, HSCOC4_PEA_1_Tll, HSCOC4_PEA_1_12, WO 2005/072050 PCT/IB2005/000433 791 HSCOC4_PEA_1_T14, HSCOC4_PEA19 T15, HSCOC4_PEA-1-T20, HSCOC4_PEA_1_T21, HSCOC4_PEA-1 T25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1-T30, HSCOC4-PEA_1_T31 and HSCOC4_PEA_lT32. Table 133 below describes the starting and ending position of this segment on each transcript. 5 Table 133 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA1 _Ti 5032 5122 HSCOC4_PEA_1_T2 5177 5267 HSCOC4-PEA_1_T3 5290 5380 HSCOC4-PEA_1_T4 5098 5188 HSCOC4_PEA_1-T5 5018 5108 HSCOC4_PEA_1_T7 4716 4806 HSCOC4-PEA-1_T8 4919 5009 HSCOC4_PEA_1_Ti 1 5968 6058 HSCOC4_PEA_1_T12 5033 5123 HSCOC4_PEA_1_T14 5312 5402 HSCOC4_PEA_1_TI5 4872 4962 HSCOC4_PEA_1_T20 5394 5484 HSCOC4-PEA-1_T21 4919 5009 HSCOC4_PEA_1_T25 4919 5009 HSCOC4-PEA_1_T28 4919 5009 HSCOC4_PEA_1_T30 4919 5009 HSCOC4_PEA_1_T31 4919 5009 HSCOC4._PEA-_1T32 4919 5009 Segment cluster HSCOC4_PEA_1_node_88 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This WO 2005/072050 PCT/IB2005/000433 792 segment can be found in the following transcript(s): HSCOC4_PEA_1-T12. Table 134 below describes the starting and ending position of this segment on each transcript. Table 134 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA-_1T12 5124 5213 5 Segment cluster HSCOC4_PEA_1_node_89 according to the present invention can be found in the following transcript(s): HSCOC4_PEA lT1, HSCOC4_PEA-lT2, HSCOC4_PEA_1_T3, HSCOC4PEA-lT4, HSCOC4_PEA_1-T5, HSCOC4_PEA_1T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_1-T12, HSCOC4_PEA-1_T14, 10 HSCOC4_PEA-lT15, HSCOC4_PEA-l_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1-T25, HSCOC4_PEAI-T28, HSCOC4-PEA_1_T30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 135 below describes the starting and ending position of this segment on each transcript. Table 135 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_-Ti 5123 5131 HSCOC4_PEA_1_T2 5268 5276 HSCOC4_PEAlT3 5381 5389 HSCOC4_PEA_1_T4 5189 5197 HSCOC4_PEAl-T5 5109 5117 HSCOC4_PEA_1_T7 4807 4815 HSCOC4_PEA_1T8 5010 5018 HSCOC4_PEA_1_Ti 1 6059 6067 HSCOC4_PEA_1_12 5214 5222 HSCOC4_PEA-1_T14 5403 5411 WO 2005/072050 PCT/IB2005/000433 793 HSCOC4_PEA_1_T15 4963 4971 HSCOC4_PEA_1_T20 5485 5493 HSCOC4-PEA_1_T21 5010 5018 HSCOC4_PEA-lT25 5010 5018 HSCOC4_PEA_1_T28 5010 5018 HSCOC4_PEA_1_T30 5010 5018 HSCOC4_PEA_1_T31 5010 5018 HSCOC4_PEA_1_T32 5010 5018 Segment cluster HSCOC4_PEA_1_node_90 according to the present invention can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1_T2, 5 HSCOC4_PEA_lT3, HSCOC4_PEA__T4, HSCOC4_PEA_1_T5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_TS, HSCOC4_PEA_1_Ti 1, HSCOC4_PEA_112, HSCOC4_PEA_1_T14, HSCOC4_PEA1_115, HSCOC4_PEA_1-T20, HSCOC4-PEA_1_T21, HSCOC4_PEA-lT25, HSCOC4PEA_1_T28, HSCOC4_PEA__T30, HSCOC4_PEA_1-T31 and HSCOC4_PEA-_T32. Table 136 below describes the starting and 10 ending position of this segment on each transcript. Table 136 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_1 5132 5142 HSCOC4_PEA_1 T2 5277 5287 HSCOC4_PEA_1_T3 5390 5400 HSCOC4_PEA_1 T4 5198 5208 HSCOC4_PEAlT5 5118 5128 HSCOC4_PEA1_1T7 4816 4826 HSCOC4_PEA_1_T8 5019 5029 HSCOC4_PEA_1_1 1 6068 6078 WO 2005/072050 PCT/IB2005/000433 794 HSCOC4_PEA_1_T12 5223 5233 HSCOC4_PEA_1_T14 5412 5422 HSCOC4-PEA_1_Ti5 4972 4Q82 HSCOC4_PEA_1 T20 5494 5504 HSCOC4_PEA_1_T21 5019 5029 HSCOC4_PEA_1_T25 5019 5029 HSCOC4_PEA_1_T28 5019 5029 HSCOC4_PEA 1_T30 5019 5029 HSCOC4_PEA_1_T31 5019 5029 HSCOC4-PEA_1_T32 5019 5029 Segment cluster HSCOC4_PEA-1_node_91 according to the present invention is supported by 78 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEAl_Ti, HSCOC4_PEAl-T2, HSCOC4_PEA-1_T3, HSCOC4-PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEAL-T7, HSCOC4_PEA-lT8, HSCOC4_PEA_1_TI 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_-T14, HSCOC4_PEAJlT15, HSCOC4_PEA-_T20, HSCOC4_PEAlT21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEAlT30, HSCOC4-PEA_-T31 and HSCOC4_PEA-lT32. Table 137 below describes the starting and ending position of this segment on each transcript. Table 13 7 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 5143 5179 HSCOC4_PEA_1 T2 5288 5324 HSCOC4_PEAI _T3 5401 5437 HSCOC4_PEA_1_T4 5209 5245 HSCOC4_PEA_1_T5 5129 5165 WO 2005/072050 PCT/IB2005/000433 795 HSCOC4_PEA_1 T7 4827 4863 HSCOC4_PEA 1 T8 5030 5066 HSCOC4_PEA-lTIl 6079 6115 HSCOC4_PEA_1T12 5234 5270 HSCOC4_PEA 1_T14 5423 5459 HSCOC4-PEA_1_T15 4983 5019 HSCOC4_PEAlT20 5505 5541 HSCOC4_PEA__T21 5030 5066 HSCOC4_PEA_1_T25 5030 5066 HSCOC4_PEA_1_T28 5030 5066 HSCOC4_PEA_1_T30 5030 5066 HSCOC4_PEA_1_T31 5030 5066 HSCOC4_PEA_1_T32 5030 5066 Segment cluster HSCOC4_PEA_1_node_92 according to the present invention can be found in the following transcript(s): HSCOC4_PEA_1_1, HSCOC4_PEA_1_T2, 5 HSCOC4_PEA_1_T3, HSCOC4_PEA_1-T4, HSCOC4_PEAAlT5, HSCOC4_PEA_1_-T7, HSCOC4_PEA-1_T8, HSCOC4-PEA1_T 11, HSCOC4_PEA_1_T12, HSCOC4_PEA_1-T14, HSCOC4_PEA_1_TI5, HSCOC4_PEA_1_T20, HSCOC4_PEAl-T21, HSCOC4_PEA_1-T25, HSCOC4-PEA_1_T28, HSCOC4_PEAIT30, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 138 below describes the starting and 10 ending position of this segment on each transcript. Table 138 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_1 5180 5197 HSCOC4_PEA_1T2 5325 5342 HSCOC4_PEA-1_T3 5438 5455 WO 2005/072050 PCT/IB2005/000433 796 HSCOC4_PEA_1_T4 5246 5263 HSCOC4_PEA_1_T5 5166 5183 HSCOC4 PEA_1_T7 4864 4881 HSCOC4_PEA _1-T 5067 5084 HSCOC4_PEA_1_Til 6116 6133 HSCOC4_PEAI_112 5271 5288 HSCOC4_PEA_1_T14 5460 5477 HSCOC4_PEA 1-Ti5 5020 5037 HSCOC4_PEAl-T20 5542 5559 HSCOC4_PEA__T21 5067 5084 HSCOC4_PEA_1_T25 5067 5084 HSCOC4_PEA_1 T28 5067 5084 HSCOC4_PEA_1_T30 5067 5084 HSCOC4_PEA_1_T31 5067 5084 HSCOC4_PEA_1_T32 5067 5084 Segment cluster HSCOC4_PEA_1_node_94 according to the present invention can be found in the following transcript(s): HSCOC4-PEA_T8, HSCOC4-PEA_112 and 5 HSCOC4_PEA_1_T21. Table 139 below describes the starting and ending position of this segment on each transcript. Table 139 - Segment location on transcripts Trancript name Segment Segment starting position ending position HSCOC4_PEA1 T8 6567 6575 HSCOC4_PEA _1T12 6771 6779 HSCOC4_PEA_1 T21 6567 6575 WO 2005/072050 PCT/IB2005/000433 797 Segment cluster HSCOC4_PEA_1_node_96 according to the present inve-ntion can be found in the following transcript(s): HSCOC4_PEA_1_T1, HSCOC4_PEAI _T2, HSCOC4-PEAIT3, HSCOC4_PEA__T4, HSCOC4_PEA-1 T5, HSCOC4_PEA-lT7, HSCOC4_PEA 1 TS, HSCOC4_PEA_1T 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, 5 HSCOC4_PEA-l_TI5, HSCOC4_PEA-T20, HSCOC4-PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4-PEA-1_T28, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 140 below describes the starting and ending position of this segment on each transcript. Table 140 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 T1 5198 5205 HSCOC4_PEA_T2 5343 5350 HSCOC4_PEA1 _T3 5456 5463 HSCOC4_PEA_1_T4 5264 5271 HSCOC4_PEA1 _T5 5184 5191 HSCOC4_PEA_T7 4882 4889 HSCOC4_PEA_1 T8 6576 6583 HSCOC4_PEA_1_TIl 6134 6141 HSCOC4_PEA1 _T12 6780 6787 HSCOC4-PEA_1_T14 5478 5485 HSCOC4_PEA_1_TI5 5038 5045 HSCOC4_PEA_1_T20 5560 5567 HSCOC4_PEA-lT21 6576 6583 HSCOC4-PEA-lT25 5085 5092 HSCOC4_PEA_lT28 5085 5092 HSCOC4_PEA_1_T31 5085 5092 HSCOC4_PEAlT32 5085 5092 10 WO 2005/072050 PCT/IB2005/000433 798 Segment cluster HSCOC4_PEA_1_node_97 according to the present invention can be found in the following transcript(s): HSCOC4_PEA_1_TI, HSCOC4_PEA_1_T2, HSCOC4-PEA_ 1T3, HSCOC4_PEA-lT4, HSCOC4_PEA-lT5, HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA_1-TI 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, 5 HSCOC4_PEA_1_T15, HSCOC4_PEA-1_T20, HSCOC4_PEA_ 1_T21, HSCOC4_PEAl-T25, HSCOC4_PEAl-T28, HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 141 below describes the starting and ending position of this segment on each transcript. Table 141 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 5206 5222 HSCOC4_PEA_1_T2 5351 5367 HSCOC4_PEA-lT3 5464 5480 HSCOC4_PEA_lT4 5272 5288 HSCOC4 PEA_lT5 5192 5208 HSCOC4_PEA_1_T7 4890 4906 HSCOC4_PEA_1_T8 6584 6600 HSCOC4_PEA_1_TI1 6142 6158 HSCOC4_PEA. 1T12 6788 6804 HSCOC4_PEA_1_T14 5486 5502 HSCOC4_PEA 1_Ti5 5046 5062 HSCOC4-PEA_1_T20 5568 5584 HSCOC4_PEA-1 T21 6584 6600 HSCOC4_PEA_1_T25 5093 5109 HSCOC4_PEA_1_T28 5093 5109 HSCOC4_PEAlT31 5093 5109 HSCOC4_PEA_1_T32 5093 5109 10 WO 2005/072050 PCT/IB2005/000433 799 Segment cluster HSCOC4_PEA-_node_98 according to the present invention is supported by 93 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA-lTi, HSCOC4_PEA-_T2, HSCOC4_PEA-lT3, HSCOC4_PEAIT4, HSCOC4_PEA_1_T5, 5 HSCOC4_PEA-_T7, HSCOC4_PEA-1_T8, HSCOC4_PEAI_TI 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1T14, HSCOC4_PEA-1T15, HSCOC4_PEA_1_T20, HSCOC4-PEAIT21, HSCOC4_PEA-lT25, HSCOC4_PEA_1_T28, HSCOC4_PEA_1_T31 and HSCOC4_PEA _T32. Table 142 below describes the starting and ending position of this segment on each transcript. 10 Table 142 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 5223 5271 HSCOC4_PEAIT2 5368 5416 HSCOC4_PEA_1_T3 5481 5529 HSCOC4_PEA_1_T4 5289 5337 HSCOC4_PEAIT5 5209 5257 HSCOC4_PEAl-T7 4907 4955 HSCOC4_PEA_1_T8 6601 6649 HSCOC4_PEAITI1 6159 6207 HSCOC4_PEA_1_T12 6805 6853 HSCOC4-PEA_1_T14 5503 5551 HSCOC4_PEA 1_TI5 5063 5111 HSCOC4_PEAIT20 5585 5633 HSCOC4_PEA_1_T21 6601 6649 HSCOC4_PEAIT25 5110 5158 HSCOC4_PEA_1_T28 5110 5158 HSCOC4_PEA_1-T31 5110 5158 HSCOC4_PEA_1_T32 5110 5158 WO 2005/072050 PCT/IB2005/000433 800 Segment cluster HSCOC4_PEA-_1node_99 according to the present invention is supported by 93 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4-PEA_1_Ti, 5 HSCOC4_PEA-I_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA-_-T4, HSCOC4_PEA_1_T5, HSCOC4_PEA-lT7, HSCOC4_PEA_1_TS, HSCOC4_PEA_1_TI1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4_PEA_1_T15, HSCOC4_PEA_1_T20, HSCOC4_PEAl_T21, HSCOC4-PEA_1_T25, HSCOC4_PEA_1_T2S, HSCOC4_PEA__T31, HSCOC4_PEAlT32 and HSCOC4_PEA_1_T40. Table 143 below 10 describes the starting and ending position of this segment on each transcript. Table 143 - Segment location on transcripts Transcript name Segment Segment starthig position ending position HSCOC4-PEA 1_Ti 5272 5300 HSCOC4_PEA 1 T2 5417 5445 HSCOC4_PEAlT3 5530 5558 HSCOC4_PEAIT4 5338 5366 HSCOC4_PEA-lT5 5258 5286 HSCOC4_PEA lT7 4956 4984 HSCOC4_PEA_1_T8 6650 6678 HSCOC4_PEA_ _TI 1 6208 6236 HSCOC4_PEA I T12 6854 6882 HSCOC4_PEA_1_T14 5552 5580 HSCOC4_PEA_1_TI5 5112 5140 HSCOC4_PEA_1_T20 5634 5662 HSCOC4-PEA_1_T21 6650 6678 HSCOC4_PEA_1_T25 5159 5187 HSCOC4_PEAl-T28 5159 5187 HSCOC4_PEAIT31 5159 5187 WO 2005/072050 PCT/IB2005/000433 801 HSCOC4_PEA-lT32 5159 5187 LHSCOC4_PEA_1_T40 4197 4225 Segment cluster HSCOC4_PEA_1_node_101 according to the present invention is supported by 116 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4_PEA.__T5, HSCOC4_PEA_1_T7, HSCOC4PEA-lT8, HSCOC4_PEA-1jII 1, HSCOC4_PEA_1_T12, HSCOC4_PEA_1T14, HSCOC4_PEAl._T15, HSCOC4_PEA_1_T20, HSCOC4_PEAl T21, HSCOC4_PEA-lT25, HSCOC4_PEA_1_T28, 10 HSCOC4_PEA_1_T30, HSCOC4-PEAl-T31, HSCOC4_PEA_1_T32 and HSCOC4_PEA_1_T40. Table 144 below describes the starting and ending position of this segment on each transcript. Table 144 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 TI 5301 5390 HSCOC4_PEA_1_T2 5446 5535 HSCOC4_PEA_T3 5559 5648 HSCOC4-PEA IT4 5367 5456 HSCOC4_PEA_1_T5 5287 5376 HSCOC4_PEA_1_T7 4985 5074 HSCOC4_PEAIT8 6679 6768 HSCOC4_PEA 1 TIl 6237 6326 HSCOC4_PEA 1_T12 6883 6972 HSCOC4_PEA_1_T14 5581 5670 HSCOC4_PEA_1_TI5 5141 5230 HSCOC4_PEAIT20 5663 5752 WO 2005/072050 PCT/IB2005/000433 802 HSCOC4_PEA_1_T21 6844 6933 HSCOC4_PEA-1_T25 5188 5277 HSCOC4_PEA_1_T28 5188 5277 HSCOC4_PEAl-T30 5085 5174 HSCOC4_PEA_ 1_T31 5188 5277 HSCOC4_PEA_1_T32 5188 5277 HSCOC4_PEAl-T40 4226 4315 Segment cluster HSCOC4_PEAInode_102 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_T31 and HSCOC4_PEA_1_T32. Table 145 below describes the starting and ending position of this segment on each transcript. Table 145 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_T31 5278 5362 HSCOC4_PEA_1_T32 5278 5362 10 Segment cluster HSCOC4_PEA_1_node_103 according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA._-T1, HSCOC4PEA_1_T2, HSCOC4_PEA9lT3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1-T5, 15 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_TS, HSCOC4_PEA_1_T1l, HSCOC4_PEAT112, HSCOC4_PEA1Y T14, HSCOC4_PEA_1-T15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA_1_T25, HSCOC4_PEA_1_T28, HSCOC4PEAlT30, HSCOC4-PEA1_-T31, HSCOC4-PEA_1_T32 and WO 2005/072050 PCT/IB2005/000433 803 HSCOC4_PEA_1_T40. Table 146 below describes the starting and ending position of this segment on each transcript. Table 146 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1_Ti 5391 5463 HSCOC4_PEA__T2 5536 5608 HSCOC4_PEA_1_T3 5649 5721 HSCOC4_PEA_1_T4 5457 5529 HSCOC4_PEA_1_T5 5377 5449 NSCOC4_PEA_1_T7 5075 5147 HSCOC4_PEA_1_T8 6769 6841 HSCOC4_PEA_1_TI1 6327 6399 HSCOC4_PEA_1_T12 6973 7045 HSCOC4_PEA-_1T14 5671 5743 HSCOC4_PEA-_1TL5 5231 5303 HSCOC4_PEA-lT20 5753 5825 HSCOC4_PEA_- T21 6934 7006 HSCOC4_PEA-lT25 5278 5350 HSCOC4_PEA_1_T28 5278 5350 HSCOC4_PEA_1_T30 5175 5247 HSCOC4-PEA_1_T31 5363 5435 HSCOC4_PEA-lT32 5363 5435 HSCOC4_PEA_1_T40 4316 4388 5 Segment cluster HSCOC4_PEA__node_104 according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEAIT1, HSCOC4_PEA_1_T2, HSCOC4_PEA-lT3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, WO 2005/072050 PCT/IB2005/000433 804 HSCOC4_PEA_1_T7, HSCOC4_PEA_1_T8, HSCOC4_PEA1_TI 1, HSCOC4 PEA_1_T12, HSCOC4_PEA_1_T14, HSCOC4-PEA-lT15, HSCOC4_PEA_1T20, HSCOC-PEAiT21, HSCOC4_PEA_1 T25, HSCOC4.PEA_1_T28, HSCOC4_PEA_-T30, HSCOC4_PEA_1_T31, HSCOC4_PEA_1_T32 and 5 HSCOC4-PEAl-T40. Table 147 below describes the starting and ending position of this segment on each transcript. Table 147 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA1 _T1 5464 5489 HSCOC4_PEA-_T2 5609 5634 HSCOC4_PEAIT3 5722 5747 HSCOC4_PEA_1_T4 5530 5555 HSCOC4_PEA_1_T5 5450 5475 HSCOC4_PEA1 _T7 5148 5173 HSCOC4_PEA_1_T8 6842 6867 HSCOC4_PEA_1 Tl 1 6400 6425 HSCOC4_PEA_1 T12 7046 7071 HSCOC4_PEA_1_T14 5744 5769 HSCOC4_PEA_1_TI5 5304 5329 HSCOC4_PEA 1_T20 5826 5851 HSCOC4_PEA_1_T21 7007 7032 HSCOC4_PEA_1_T25 5351 5376 HSCOC4_PEA_1 T28 5351 5376 HSCOC4_PEA_1_T30 5248 5273 HSCOC4_PEA_1_T31 5436 5461 HSCOC4_PEA1_T32 5436 5461 HSCOC4_PEA_1_T40 4389 4414 WO 2005/072050 PCT/IB2005/000433 805 Segment cluster HSCOC4_PEA_1_node_106 according to the present invention is supported by 110 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA 1 T1, HSCOC4_PEA_1_T2, HSCOC4PEA_1_T3, HSCOC4_PEA_1_T4, HSCOC4_PEA_1_T5, 5 HSCOC4_PEA_1_T7, HSCOC4_PEA-lT8, HSCOC4_PEA_1 Tl 1, HSCOC4_PEAl_T12, HSCOC4_PEA_1T14, HSCOC4PEA-lT15, HSCOC4_PEA_1_T20, HSCOC4_PEA_1_T21, HSCOC4_PEA _IT25, HSCOC4_PEA 1_T28, HSCOC4_PEA_1_T30, HSCOC4_PEA_1-T31, HSCOC4_PEA_1_T32 and HSCOC4_PEAIT40. Table 148 below describes the starting and ending position of this 10 segment on each transcript. Table 148 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 Ti 5490 5573 HSCOC4_PEA_1_T2 5635 5718. HSCOC4_PEA_1_T3 5748 5831 HSCOC4_PEAIT4 5556 5639 HSCOC4_PEA-1_T5 5476 5559 HSCOC4_PEA_1_T7 5174 5257 HSCOC4_PEA- 1T8 6868 6951 HSCOC4_PEA_1_TI 1 6426 6509 HSCOC4_PEA_1_T12 7072 7155 HSCOC4_PEA_1_T14 5770 5853 HSCOC4_PEA_1_TI5 5330 5413 HSCOC4_PEA_1_T20 5852 5935 HSCOC4_PEA1_T21 7033 7116 HSCOC4_PEA_1_T25 5377 5460 HSCOC4_PEA_1_T28 5559 5642 HSCOC4_PEA-1_T30 5274 5357 WO 2005/072050 PCT/IB2005/000433 806 HSCOC4_PEA-1_T31 5 4 62 5545 HSCOC4_PEA-lT32 5644 5727 HSCOC4_PEA _1_T40 4415 4498 Segment cluster HSCOC4JPEA_1_node_ 1I according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HSCOC4_PEA_1_Ti, HSCOC4_PEA_1_T2, HSCOC4_PEA-lT3, HSCOC4_PEA-lT4, HSCOC4_PEA_1_T5, HSCOC4_PEA._lT7, HSCOC4_PEA_1-TS, HSCOC4_PEA_1_Til, HSCOC4_PEA_1_T12, HSCOC4_PEA_19T14, HSCOC4-PEA_1-T15, HSCOC4_PEA_1_T20, HSCOC4_PEA _T21, HSCOC4_PEA1_T25, HSCOC4_PEA_1_T28, 10 HSCOC4-PEAlT30, HSCOC4_PEA_19T31, HSCOC4_PEA1_T32 and HSCOC4_PEA__T40. Table 149 below describes the starting and ending position of this segment on each transcript. Table 149 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSCOC4_PEA_1 TI 5857 5947 HSCOC4_PEA_1 T2 6002 6092 HSCOC4_PEA_1_T3 6115 6205 HSCOC4_PEA_T4 5923 6013 HSCOC4_PEA_1_T5 5843 5933 HSCOC4_PEA-_T7 5541 5631 HSCOC4_PEA_1 T8 7235 7325 HSCOC4_PEA-1_Ti 1 6793 6883 HSCOC4_PEA_1_T12 7439 7529 HSCOC4_PEA_1_T14 6137 6227 HSCOC4_PEA_1_TI5 5697 5787 WO 2005/072050 PCT/IB2005/000433 807 HSCOC4_PEA_1_T20 6219 6309 HSCOC4_PEA_1_T21 7400 7490 HSCOC4_PEA_1_T25 6149 6239 HSCOC4_PEA_1_T28 6331 6421 HSCOC4_PEA_1_T30 5641 5731 HSCOC4_PEA_1_T31 5829 5919 HSCOC4_PEA_1_T32 6273 6363 HSCOC4_PEA_1_T40 4782 4872 Variant protein alignment to the previously known protein: 5 Sequence name: C04_HUMAN Sequence documentation: Alignment of: HSCOC4 PEA 1 P3 x C04_HUMAN 10 Alignment segment 1/1: Quality: 8438.00 Escore: 0 15 Matching length: 870 Total length: 870 Matching Percent Similarity: 99.66 Matching Percent Identity: 99.66 Total Percent Similarity: 99.66 Total Percent 20 Identity: 99.66 Gaps: 0 Alignment: WO 2005/072050 PCT/IB2005/000433 808 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 5 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 10 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 20 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 25 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 30 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 WO 2005/072050 PCT/IB2005/000433 809 351 EMEEAELTSVYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 5 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 10 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 15 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 25 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 30 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 WO 2005/072050 PCT/IB2005/000433 810 | | | | | | 1 |1 |||| | | | || | | | | 111 1|| | | | | |1 | | | | | ||11 111 | | 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 5 |||||1I11 |||| ||||| ||1|1 |||1|||| ||||1||| |||t 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVRPHRS 870 |11|||||||||||| | | 10 851 LRPVLYNYLDKNLTVSVHVS 870 15 Sequence name: C04_HUMAN Sequence documentation: 20 Alignment of: HSCOC4_PEA_1 P5 x C04_HUMAN Alignment segment 1/1: 25 Quality: 7969.00 Escore: 0 Matching length: 818 Total length: 818 Matching Percent Similarity: 100.00 Matching Percent 30 Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 811 Total Percent similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 10 - 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 15 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 25 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 30 - - - 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 WO 2005/072050 PCT/IB2005/000433 812 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 5 | | | | | | | | | | | | | | | | | | | l| | | | | | | | | | | | | | | | | | | | | 1 l1| | | 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 10 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 15 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 20 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 | | | ||1 | | | | | | | | | | l I | | | | | | | | | | | | | | 1 | | | | | | | | | | | 7 30 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 WO 2005/072050 PCT/IB2005/000433 813 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 5 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKG 818 10 | | | | | | | | | 801 DSLTTWEIHGLSLSKTKG 818 15 Sequence name: C04_HUMAN 20 Sequence documentation: Alignment of: HSCOC4_PEA_1_P6 x C04_HUMAN Alignment segment 1/1: 25 Quality: 10211.00 Escore: 0 Matching length: 1052 Total length: 1052 30 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 814 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 10 - - 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 15 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 25 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 30 - - - 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 WO 2005/072050 PCT/IB2005/000433 815 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 5 1 | | | | | | | | | | | | | | | | | | | | | I l l i I 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 1| | | | | | | | | | | | i 1|| | | | | | | | | | | 1 | | | 1| | | | | | | | | | 1 1 1 | | 10 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 li llll111lllllllllllllllllllll~ll l~l|| | | || | | | |1 | 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 15 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 1 l l l l l l l l l l l l l l i 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 20 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 25 1|| |1|| | | I1| |1|| | | | |1 1|| | | | | | | | | | | | | | | | | | | I 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 30 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 WO 2005/072050 PCT/IB2005/000433 816 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 | | | | | | | | | | l1 i l 1 1 1 1 l l I | | | | | | | |1|| | | |1|| | | | l 11| | | | | | 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 5 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 10 I I|| || | Il l |1 1| | | | | | | | |1 I I 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 |||| |l l I l il1 ||1l ll11ll1ll111l l11 1 1 1 i| || ||1 1 ||||||11 15 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 I l 1 l1i I | | | | | | | | | | | | | | | | | | | | 1 1 1 1 | I 1 1 1 | | | | | | | | | | | 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 20 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 25 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 | | | | | | | | | | | I I I 11l l l l 11ll11ll1 lI l 1 l I| | | | | | | | | | | | | | | | | 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KG 1052 30 1| 1051 KG 1052 WO 2005/072050 PCT/IB2005/000433 817 5 Sequence name: C04_HUMAN_V1 Sequence documentation: 10 Alignment of: HSCOC4_PEA_1_P12 x C04_HUMAN_V1 Alignment segment 1/1: 15 Quality: 13367.00 Escore: 0 Matching length: 1380 Total length: 1380 Matching Percent Similarity: 100.00 Matching Percent 20 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 30 - - - 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 WO 2005/072050 PCT/IB2005/000433 818 |||||||||| 11 1 11 1|| | | | | | | | |1 |||||||||III 111||||| 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 5 |i|i|| il ||| |1111| 1 | || ||| |i|l |1|| | 1||||| ||1| 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 10 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 15 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 il lil l l llllllllllll lill l lli lt l i|||||||||||1 ||||1 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 20 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 25 |l|l|i| | | 1 | || | il| | | lilt | | | 1 | | | 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 30 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 WO 2005/072050 PCT/IB2005/000433 819 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 5 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 | | 1 1 | 1 | | | | | | |1|| | | | | | | | | | | | 1| | | | | | | | | | | | | | | | | | | 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 10 1 1 1 1 1 11i| | | | | | | | | | | | | | | | | | 1|| | | | |1| | I | | | | | | | | | | 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 i l 11|| || |11|| | | | | | | | | | | | | | |1 1i ll ll l l1ll 11l 11| | 15 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 | | 1 11 11 | | | | | | || | || 11 | |1 i | | | | | |1 | | | | | | || | | | | | 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 20 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | l lI l 1l1l 1 l 1i| | | | | | 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 25 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 30 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 WO 2005/072050 PCT/IB2005/000433 820 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVjVPAGSARPVAFS 900 11l11i1l 11l1li 1I1ll|| 1l1l| ||||| |l ll l ||||1 I 1||||||||||| 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 5 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 I I | | | | I| | | | ||||I 1 | | | | | | |I1l 11 1 i 1 I 1l11l 11||I l | | || |-|| | | | | 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 10 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 || I1ll|||1 |||||1 ||||||11 1| 1 ||||11 I |||l 11 I| I i I|| 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 15 | |1 | | |1 | | | | ||1 | | ||1 | | 1 |1 | 1| I I | | I | || | | || | 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 20 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 25 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1111i I|| 11i 11 i l l1i111 i11|| |||||||| |||||||| |||||||| 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 30 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 | | | | l i l i | | | l l 1i1i 1 11i lII| | | | | | | | | | II|| | | | | | I l l WO 2005/072050 PCT/IB2005/000433 821 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 5 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 10 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKV 1380 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKV 1380 15 20 Sequence name: C04_HUMANV1 Sequence documentation: Alignment of: HSCOC4_PEA_1 P15 x C04_HUMAN_V1 25 Alignment segment 1/1: Quality: 13174.00 Escore: 0 30 Matching length: 1359 Total length: 1359 WO 2005/072050 PCT/IB2005/000433 822 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 10 | 1| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |11 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 | | | | | | | | | | | | | | | | | | | | | | | | | | | |1 | | ||I. 1 | | | ||1 1 1 1 1 | | |1 | |I 15 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 20 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 25 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 WO 2005/072050 PCT/IB2005/000433 823 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAILESPGG 350 | |i | | | | | | 1 1 | | | | | | | | | ||11 1 | ||II | | | ||I | | | | | | | | | I | | | | | | 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 5 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 10 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 | | |1 | | | | | | | | | | | | | | | | | 1 11| | | |1 | | | | | | | | | | | | | | ||1 1 | 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 15 | | | | | | | | | | | | 1 | | | | |1 | | | | | | | | | | ||1 | | | | | | | |1 | | | | | | | 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 20 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA. 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 25 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 iIII| | | | | | | | | | | | | | | | | | l 1l | | | | | | | | | | | | | | | 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 30 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l1 | | | | | | | | | | | | | | I | WO 2005/072050 PCT/IB2005/000433 824 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 11|||||||111|1||||i1|||||||||||1||||||||||||||||11 5 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 10 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 15 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 2 0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |l1 l l l l l l l l | | | 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 ||||||||||||||||||||||||||||||||||||||||||||||||||I 25 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 lillllllllllllllllllllllllllllll ||||||||||||||||| 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 30 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 WO 2005/072050 PCT/IB2005/000433 825 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 5 | | | | | | |1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 10 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 15 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 20 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1351 IRGLEEELQ 1359 25 111111111 1351 IRGLEEELQ 1359 30 WO 2005/072050 PCT/IB2005/000433 826 Sequence name: C04 HUMAN V1 Sequence documentation: 5 Alignment of: HSCOC4_PEA_1_P16 x C04_HUMAN V1 Alignment segment 1/1: 10 Quality: 14137.00 Escore: 0 Matching length: 1457 Total length: 1457 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 25 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 li l l l l l l l l l l I ll l l l l l l l l l l l l l ll l l l l l l l l l l l l l l l l i l 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 30 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 l i l l l l l l l l l l l l l1 1 ll l l l l l l l l l ll l l l l l l l l l l i l l l i i I WO 2005/072050 PCT/IB2005/000433 827 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l f i l l lli 5 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 10 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 15 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 fl l fl l l l l l l l l l l l l l l l l l l1 ffl l l l l l lffl l l l l l l l l l l l l l l l i 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 20 | | | | | | f| | | | | | | | | | | | | | | f| | | | | | | | | | 1| 1| 1| | | | | | | | | | | | 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 25 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l lff l l l ll l 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 30 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 WO 2005/072050 PCT/IB2005/000433 828 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 10 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 15 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 20 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 2 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 30 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 WO 2005/072050 PCT/IB2005/000433 829 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 5 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 l i l l l l l l l l l l l l l l l l l l l l l l | 1 | | | | | | | | | | | 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 10 1 1 1 11|| | | | | | | | | | | | | | | | | |1 | | | | | | | | | | | | | | | | | | | | | 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 l l l l l l l l l l l l l l l lll l l l l l l l l l l l l l l 15 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 20 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 25 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 WO 2005/072050 PCT/IB2005/000433 830 1301 STQDTVIALDALSAYWIASHTTEERGLNTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 5 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 | | | | | | | | | |i 1 | | | | | | | | | | | | | | | | | | l l1l 1l l l l l l l l l l1 l l 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 10 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPK 1457 15 . 1| ||| 1451 RRREAPK 1457 20 Sequence name: C04_HUMAN_V1 25 Sequence documentation: Alignment of: HSCOC4_PEA_1_P20 x C04 HUMANV1 Alignment segment 1/1: 30 WO 2005/072050 PCT/IB2005/000433 831 Quality: 12641.00 Escore: 0 Matching length: 1303 Total length: 1303 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 15 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 20 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 25 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 30 |I | I | 11111|1| 1 111 1 1|| 11 | | 1|| || |||| | | | | |0 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 WO 2005/072050 PCT/IB2005/000433 832 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 ||l i l 11 11 11 11 ii I Il || | | | | || | | | | | 1 | | 1 1 ||||||11 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 5 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 ||||I li| || |||||| | | |||1|| | | |1 1 || ||I1l1 l l l li l ll l 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 10 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | I l1 1| | | | | | | | | | | 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 15 | | | | | | | | I I | | I | | |1|| | |1 | | | | | | | | | | | | | 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 20 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 25 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 30 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 WO 2005/072050 PCT/IB2005/000433 833 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 I I|1 |||||||||||||||1 1 I 11|||1 l1l1I1 l1l1il 1l1i 1|||||| I l 5 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 111111 li I11 11 1 11 11|1111|| 1 | 1I | | | |1 |||||||i I I I l 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 10 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 15 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 20 1111 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 25 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 30 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 WO 2005/072050 PCT/IB2005/000433 834 ||||||||||| 11|| | | |1 |||||I11 1 11 11||1|| | 1 11 || || 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 5 ||||1 I l1l 1|| || 1 1 1 |||||| 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 10 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 15 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 20 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQ 1303 25 |1| 1301 STQ 1303 30 WO 2005/072050 PCT/IB2005/000433 835 Sequence name: C04_HUMANV1 Sequence documentation: 5 Alignment of: HSCOC4_PEA_1_P9 x C04_HUMANVi Alignment segment 1/1: 10 Quality: 14831.00 Escore: 0 Matching length: 1529 Total length: 1529 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 25 . . . . 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 30 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 WO 2005/072050 PCT/IB2005/000433 836 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 5 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 | | | | | | | | | | | | | | | | | | | | | l1 1l | | | 1 i i i 1 1 I I l I i l l i l l l 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 10 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 15 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 1 1 l i | | | | | | | | | | | | | 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 20 | || || || || | | 1 1 1 11 | l | | | 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 25 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 30 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 WO 2005/072050 PCT/IB2005/000433 837 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 5 | | | | | | | | | | | | | | 1| | | | | | | | | | | | | | | | | | | 1 | 1 | | | | | | | | | 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 11 11| 1 |1|| |||||| ||||| 1|| 11 |1 l lill l llll I l ll| || 10 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 15 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 1 | | | | | | |I1 l I I I1 I | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 20 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 i i 1i 1 1| | | | | | | | | |I I | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 25 | | | | | 11|1|| 11 |||||1 11 | 1111111 | | 1|| ||| | | | 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 l0 8 51 II| | | | | I l l i | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 30 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGL.AQQVLVPAGSARPVAFS 900 WO 2005/072050 PCT/IB2005/000433 838 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 5 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1 0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 15 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 20 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKAS$FLGEKASAGLLGAHAAAITAYAL 1200 25 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 WO 2005/072050 PCT/IB2005/000433 839 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 l i l1 l l1 l l l l l l l l l l 1 | | | | | | ||II 1 | | | | | | | | | | | | | | | | | | | 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 5 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 10 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1 5 l I | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | I|| | | | | 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529 20 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529 25 Sequence name: C04_HUMANV1 Sequence documentation: 30 Alignment of: HSCOC4_PEA_1_P22 x C04_HUMAN_V1 l .

WO 2005/072050 PCT/IB2005/000433 840 Alignment segment 1/1: Quality: 16066.00 5 Escore: 0 Matching length: 1654 Total length: 1654 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.94 10 Total Percent Similarity: 100.00 Total Percent Identity: 99.94 Gaps: 0 Alignment: 15 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 20 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 25 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 30 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 WO 2005/072050 PCT/IB2005/000433 41 201 DFVIPDISEPGTWKISARFSDGLES3NSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 5 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 l i l l l 1 1l l 1l l l l 1ll l l l l l l l l ll l l l l l l l l l l l l l l l l l l l l l l 15 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 20 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 25 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNCESVKLHLETDSLALVA 600 30 |||||||||||||||||||||| |||||||1111|||| 1||||| 11||||1| 0 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALJVA 600 WO 2005/072050 PCT/IB2005/000433 842 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 5 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 10 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQPALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 15 | | 11| 1 || | 1 1| | | | | 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 20 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 25 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 30 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 I I | | | | | | | | | | | | | | | | | | | 1 l |1 | | | I | | | | | |1 | | | | ||1 1 WO 2005/072050 PCT/IB2005/000433 84 3 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 | | || | | || | | | | |||1 I li l | | | | | I l I 1 1 l | | | | | | | | | | | | | 5 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 10 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 15 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 20 |I|l|Il|1| 1 | | 11 1 111111 | IIII II 11111 | III | | 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 25 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 30 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 WO 2005/072050 PCT/IB2005/000433 844 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 5 | | | |1|| | | | | | | |l|l | | 1| | | | | | i| | | | | | | | | | | | | 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 10 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 |1 1 111111 | 1|| 1 1||||11||1 ||il ||||||||i |1 ||||||1 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 15 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600 20 1601 ALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAFRLFETKITQV 1650 1601 ALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAFRLFETKITQV 1650 1651 LHFS 1654 25 i||: 1651 LHFT 1654 30 WO 2005/072050 PCT/IB2005/000433 845 Sequence name: C04_HUMANV1 Sequence documentation: 5 Alignment of: HSCOC4_PEA_1 P23 x C04_HUMAN_V1 Alignment segment 1/1: 10 Quality: 15806.00 Escore: 0 Matching length: 1626 Total length: 1626 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 25 - - - 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 30 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l WO 2005/072050 PCT/IB2005/000433 846 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 | | | | | | | | | | | | | | |1 | | | | | | | | | | | | ||11 l l l l l1 1 1 I l l1 l1 5 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 10 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 15 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 20 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 I l i l l l l l l l l l l Ill l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 25 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 30 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 WO 2005/072050 PCT/IB2005/000433 847 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 5 I | l| | II|| I|| I | 1 |1|1 |1| 1| | ||||||||| | | | 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 | | | | | | 1 IiiI| | |1|| | | | | | | | | | | | | | | | |1 | |1 1 10 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 | | | I l l i | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 1 1 I | | | | | | | | 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 15 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 20 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 2 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |1 I| | | | | | | 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 30 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 WO 2005/072050 PCT/IB2005/000433 848 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 5 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 | | | | | | | | | | | | | | |II l l i 1 1I | | | | | | | | | | | | | | | | | | | | | | | 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 15 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 20 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 25 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 WO 2005/072050 PCT/IB2005/000433 849 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 5 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 10 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1451 RRREAPKVVEEQESRVHYTVCIWRNGK VGLSGMAIADVTLLSGFHALRAD 1500 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 20 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAVCQCAEGKCPRQRR 1600 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600 25 1601 ALERGLQDEDGYRMKFACYYPRVEYG 1626 1601 ALERGLQDEDGYRMKFACYYPRVEYG 1626 30 WO 2005/072050 PCT/IB2005/000433 850 Sequence name: C04_HUMANV1 5 Sequence documentation: Alignment of: HSCOC4_PEA_1_P24 x C04_HUMAN_Vl 10 Alignment segment 1/1: Quality: 14823.00 Escore: 0 Matching length: 1528 Total 15 length: 1528 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 20 Gaps: 0 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 2 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1| | | | | | | | | | | | | | | 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 30 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 WO 2005/072050 PCT/IB2005/000433 851 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 5 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 10 | | | | | | | | | | | | | | 1 | | | | | | | | | | | | | | | | | | | | | | | |1 | | |1 | | |1 | | 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 15 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYTV-AAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 20 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 25 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLPAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 WO 2005/072050 PCT/IB2005/000433 852 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 5 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 10 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 15 | l l l l l l l i l l l l l l l l l l l l l l l l l | | | | l l l l l l l l l l l l l l l l1 1 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 20 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 25 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 30 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 | | | | | | | | | | | ||1 1 WO 2005/072050 PCT/IB2005/000433 853 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 ||||||||| 1 11 1|| | | | | | | | 111111 ||111|||||||||||||| 5 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 10 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 15 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 20 | | | 1|1| ||||||||1|| | | | | |1|1|1||1| | 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 25 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLLMAAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 30 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 WO 2005/072050 PCT/IB2005/000433 854 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 5 I 1| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |l | | | | | | 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 10 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 15 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 20 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDS 1528 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDS 1528 25 Sequence name: C04_HUMAN_V1 30 Sequence documentation: WO 2005/072050 PCT/IB2005/000433 855 Alignment of: HSCOC4_PEA 1_P25 x C04_HUMANV1 Alignment segment 1/1: 5 Quality: 15464.00 Escore: 0 Matching length: 1593 Total length: 1593 10 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 20 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 25 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 30 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 | | | | | | | | ||iii | | | | 11 | | | | | | | | | | | | |I | | I l l i l I | | WO 2005/072050 PCT/IB2005/000433 856 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 1||||||||||||1|||||11|1111|11|1|||||||||||||||||1 5 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 10 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 II l i il l l i l li l l l l l l l l l l l l l l l l ll1| | | | | | | | | | | | |1 | |1 1 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 15 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 25 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 30 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 WO 2005/072050 PCT/IB2005/000433 857 || 1 11 111|| ||||||| 1| |1 |1 |1 II l 1l I 1 I| || 1 I||1 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 5 || | | | | || | | |1|| |1|1 1 1 1| | | || | |1 | 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 10 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 15 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 20 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 2 5| | | | | | | | 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 | | l9l0i | | | ||1 l lT i I I l l i l l i l l | | | | | | | | | |1 | | | | | | | | 9 30 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 WO 2005/072050 PCT/IB2005/000433 858 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 | | | | | | | | | | | | | | | | | | l1 l1 1 1 1| | | | | | | | | | | | | | | | | | | | |I li l I I 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 5 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 101| 1| | | | | | | | | | | | | | | | | | | | | 1| | | | | | | | | |I | | | | |1 | | | | | | | | 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 15 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 20 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 25 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 30 |301 | | | | | | 1| | | || 1| | 1| | || 1|1| || 1 |||||| ||5| 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 WO 2005/072050 PCT/IB2005/000433 859 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 5 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 | | | | | || | | | ||11 1 I | | | | | | || | | | 111 I |1 | | | | | | | ||1 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 10 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593 20 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593 25 Sequence name: C04_HUMAN_V1 Sequence documentation: 30 Alignment of: HSCOC4_PEA_1_P26 x C04_HUMAN_Vi WO 2005/072050 PCT/IB2005/000433 860 Alignment segment 1/1: Quality: 15464.00 5 Escore: 0 Matching length: 1593 Total length: 1593 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 - - 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 20 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 l i l l i l l i l l l l l i l l l l l i l l l l li l l l i l l l i l l l l l i l l l l l l li1 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 3 0 1 51 i | | | | | | | | | | | | | | | | | I|| | | | | | | | | | | | | | | l I | | | | | | | | 30 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 WO 2005/072050 PCT/IB2005/000433 861 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 5 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 15 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 20 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 25 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 WO 2005/072050 PCT/IB2005/000433 862 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 5 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 10 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 20 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS. 900 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 25 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 30 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 WO 2005/072050 PCT/IB2005/000433 863 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 || 1 11 1 1 1||||||||||||1||1|| | | |1 ||||1 |||||||||||| 5 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 | | |1 11|1 | | | | | I 11 1| | | | | || | | 111 1 | || | | | ||11 | || | | | ||1 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 10 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 15 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 25 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 30 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 WO 2005/072050 PCT/IB2005/000433 864 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 10 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550 15 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593 1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593 20 25 Sequence name: C04_HUMANV3 Sequence documentation: Alignment of: HSCOC4_PEA_1_P30 x C04_HUMANV3 30 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 865 Quality: 11940.00 Escore: 0 Matching length: 1232 Total 5 length: 1232 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 10 Gaps: 0 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 20 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 25 - - - 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 ||||| ||||| i llI | | || | | | 1 1 1 1 1 1 1 I I I 11 1 1 1 ll i | 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 30 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 ||||||||||||1 I I I i l 1 1 11 I I | || | | l | | | |1 ||||||1 WO 2005/072050 PCT/IB2005/000433 866 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 5 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 10 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 15 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 25 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 30 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 WO 2005/072050 PCT/IB2005/000433 83 6) 7 I||||| ||||||1 ||||||| Ji l 1 1|| || | |1 |1 ||||||||II 601 LGALDTALYAAGSKSHKPLNMGKV FEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 5 l i l l l l l l l l l l l l l l l l l l l l l l l i l l l l l l l l l l l l l l l l l l 651 GIAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQPAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 10 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 1il1l1ll11lllll1l1lllllllllll1llllll1llllllllllll| 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 15 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 20 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 3i 91 L l l l l l l l l l l l l l l l l l l l l l l l l l | | | | | | | | | | | | | | 1| | 30 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 WO 2005/072050 PCT/IB2005/000433 868 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 5 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 15 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 1232 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 1232 20 25 Sequence name: C04_HUMAN Sequence documentation: 30 Alignment of: HSCOC4_PEA_1_P38 x C04_HUMAN .

WO 2005/072050 PCT/IB2005/000433 869 Alignment segment 1/1: Quality: 7969.00 Escore: 0 5 Matching length: 818 Total length: 818 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 1.00.00 Gaps: 0 Alignment: 15 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 25 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 30 - - 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 WO 2005/072050 PCT/IB2005/000433 870 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 10 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 15 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 20 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 30 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 WO 2005/072050 PCT/IB2005/000433 871 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 | 1| |11 1 1| 1| 1 |1 ||11 ||1|1 1111| 1 i l 11i 1 l 11i 1 l lll 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 5 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 15 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKG 818 801 DSLTTWEIHGLSLSKTKG 818 20 25 Sequence name: C04_HUMAN Sequence documentation: 30 Alignment of: HSCOC4_PEA_1_P39 x C04_HUMAN WO 2005/072050 PCT/IB2005/000433 872 Alignment segment 1/1: Quality: 3766.00 Escore: 0 5 Matching length: 387 Total length: 387 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 25 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 30 - 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 WO 2005/072050 PCT/IB2005/000433 873 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 5 ||1||||||11111 llIll I llIlli l l 111| | 1 | | 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 10 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ 387 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ 387 15 20 Sequence name: C04_HUMAN Sequence documentation: 25 Alignment of: HSCOC4_PEA_1_P40 x C04_HUMAN Alignment segment 1/1: Quality: 2309.00 30 Escore: 0 WO 2005/072050 PCT/IB2005/000433 874 Matching length: 236 Total length: 236 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 10 - 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 15 51 V\KGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 2 0 | | l l l l l l1 l l l l l l l l l l l l l l l l l l l l l ll1 | | | | | | |1 | | | | | | | | | 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 25 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY 236 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY 236 30 WO 2005/072050 PCT/IB2005/000433 875 5 Sequence name: C04_HUMAN_V1 Sequence documentation: Alignment of: HSCOC4_PEA_1 P41 x C04_HUMAN_Vi 10 Alignment segment 1/1: Quality: 14831.00 Escore: 0 15 Matching length: 1529 Total length: 1529 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 20 Identity: 100.00 Gaps: 0 Alignment: 25 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKAKSCGLH 100 30 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 WO 2005/072050 PCT/IB2005/000433 876 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 5 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 10 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 15 I l l l l l l l l l l l l l ll1l l l l l l l l l l l l l l l l l l l l l l l l lI l l l1 l1 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 lI l l l l l l l l l l l l l l l l l l l l l l l l l l1 1 1ll l l l l l l l l l l l l l l l l l i 20 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 25 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 30 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 l I l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i WO 2005/072050 PCT/IB2005/000433 877 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 5 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 10 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 15 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 25 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 30 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 WO 2005/072050 PCT/IB2005/000433 878 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 5 |||||||||||||| || 1I1l l11|| |||||1|1|| I I li| i I 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 10 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 15 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 20 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 30 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 WO 2005/072050 PCT/IB2005/000433 879 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 5 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 15 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALPD 1500 1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500 20 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529 1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529 25 30 Sequence name: C04_HUMANVI WO 2005/072050 PCT/IB2005/000433 880 Sequence documentation: Alignment of: HSCOC4_PEA_1_P42 x C04_HUMAN V1 5 Alignment segment 1/1: Quality: 14480.00 Escore: 0 Matching length: 1506 Total 10 length: 1544 Matching Percent Similarity: 99.93 Matching Percent Identity: 99.87 Total Percent Similarity: 97.47 Total Percent Identity: 97.41 15 Gaps: 1 Alignment: 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 201| 1| | 1 1 | | | | | | |1 | | | | | | | | | | | | | | | | | | | | | | | | |1 | |1 | | | 1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 25 51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150 30 - - - 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 WO 2005/072050 PCT/IB2005/000433 881 151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 10 251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350 15 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400 20 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 30 501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550 WO 2005/072050 PCT/IB2005/000433 882 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600 5 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 15 701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800 20 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850 25 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 30 Ill 901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950 WO 2005/072050 PCT/IB2005/000433 883 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000 5 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050 10 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 15 | | | | | | 1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 20 1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250 25 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300 30 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 ||||||||||| 1 111||||||||||||||1 1111|||||| WO 2005/072050 PCT/IB2005/000433 884 1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 5 1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450 10 - 1451 RRREAPKVVEEQESRVHYTVCIWWAPGAALGQGREGRTQAGAGLLEPAQA 1500 1451 RRREAPKVVEEQESRVHYTVCIW ........................... 1473 15 1501 EPGRQLTRLHRRNGKVGLSGMAIADVTLLSGFHALRADLEKVWS 1544 | | | | | | | | | | | 1 | | | | | | |1 | | | | | | | | |1 : I 1474 ............. RNGKVGLSGMAIADVTLLSGFHALRADLEKLTS 1506 DESCRIPTION FOR CLUSTER HUMTREFAC 20 Cluster H1UMTREFAC features 2 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. HUMTREFACPEA_2_T4 507 HUMTREFACPEA_2_T5 508 25 Table 2 - Segments of interest Segment Name Sequence ID No.

WO 2005/072050 PCT/IB2005/000433 885 HUMTREFACPEA_2_node_0 509 HUJMTREFACPEA_2 node_9 510 HUMTREFAC PEA_2-node_2 511 HIUMTREFACPEA_2_node_3 512 HUMTREFACPEA-2_node_4 513 HUMTREFAC.PEA_2_node_5 514 HUMTREFACPEA_2_node_8 515 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) HUMTREFACPEA2 P7 517 HUMTREFACPEA_2_T5 HUITREFACPEA_2 P8 518 HUMTREFACPEA_2_T4 These sequences are variants of the known protein Trefoil factor 3 precursor (SwissProt 5 accession identifier TFF3_HUMAN; known also according to the synonyms Intestinal trefoil factor; hPl.B), SEQ ID NO: 516, referred to herein as the previously known protein. Protein Trefoil factor 3 precursor is known or believed to have the following function(s): May have a role in promoting cell migration (motogen). The sequence for protein Trefoil factor 3 precursor is given at the end of the application, as "Trefoil factor 3 precursor amino acid 10 sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 74-76 QEA -> TRKT Protein Trefoil factor 3 precursor localization is believed to be Secreted. The following GO Annotation(s) apply to the previously known protein. The following 15 annotation(s) were found: defense response; digestion, which are annotation(s) related to Biological Process; and extracellular, which are annotation(s) related to Cellular Component.

WO 2005/072050 PCT/IB2005/000433 886 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 5 Cluster HUITREFAC can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 36 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to 10 the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 36 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues, breast 15 malignant tumors, pancreas carcinoma and prostate cancer. Table 5 - Normal tissue distribution Name of Tissue Number adrenal 40 colon 797 epithelial 95 general 39 liver 0 lung 57 lymph nodes 3 breast 0 muscle 3 pancreas prostate 16 stomach 0 WO 2005/072050 PCT/IB2005/000433 887 Thyroid 257 uterus 54 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue, PI P2 SPI R3 SP2 R4 adrenal 6.4e-01 6.9e-01 7.le-01 1.1 7.8e-01 0.9 colon 4.6e-01 5.7e-01 9.7e-01 0.5 1 0.4 epithelial 2.4e-02 3.4e-01 9.5e-10 2.0 5.3e-02 1.1 general 2.5e-04 3.9e-02 1.4e-28 3.6 1.9e-10 1.9 liver I 6.8e-01 1 1.0 6.9e-01 1.4 lung 4.8e-01 7.6e-01 2.2e-03 1.0 1.6e-01 0.5 lymph nodes 5.le-01 8.Oe-0l 2.3e-02 5.0 1.9e-01 2.1 breast 7.6e-02 1.2e-01 3.le-06 12.0 1.le-03 6.5 muscle 9.2e-01 4.8e-01 1 0.8 3.9e-01 2.1 pancreas 1.2e-01 2.4e-01 5.7e-03 6.5 2.le-02 4.6 prostate 1.5e-01 2.7e-01 9.9e-10 8.1 3.le-07 5.7 stomach 3.0e-01 1.3e-01 5.0e-01 2.0 6.7e-02 2.8 Thyroid 6.4e-01 6.4e-01 9.6e-01 0.5 9.6e-01 0.5 uterus 4.le-01 7.3e-01 7.5e-02 1.3 4.0e-01 0.8 As noted above, cluster HUIMTREFAC features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Trefoil factor 3 5 precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMTREFACPEA_2_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 HUMTREFACPEA_2_T5. The location of the variant protein was determined according to results ftom a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both WO 2005/072050 PCT/IB2005/000433 888 signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction progr am predicts that this protein has a trans-membrane region. Variant protein HLMTREFACPEA_2_P7 also has the following non-silent SNPs 5 (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HULMTREFACPEA_2_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 7 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 5 A ->S No 5 A ->T No 14 A->V Yes 43 L->M No 60 P->S Yes 123 S->* Yes Variant protein IUMTREFACPEA_2_P7 is encoded by the following transcript(s): HUMTREFACPEA_2_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTREFACPEA_2_T5 is shown in bold; this coding 15 portion starts at position 278 and ends at position 688. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMTREFACPEA_2-P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 8 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 889 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 233 A-> G Yes 290 G -> A No 290 G->T No 318 C -> T Yes 404 C -> A No 404 C -> T No 455 C -> T Yes 645 C -> A Yes 685 C->T No Variant protein HUMTREFACPEA_2_P8 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HLUMITREFACPEA_2_T4. An alignment is given to the known protein (Trefoil factor 3 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between H4UMTREFACPEA-2_P8 and TFF3_HUMAN: 1.An isolated chimeric polypeptide encoding for HUMTREFACPEA_2_P8, comprising a first amino acid sequence being at least 90 % homologous to MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1 - 27 of TFF3_HUMAN, which also corresponds to amino acids 1 - 27 of HURMTREFACPEA_2-P8, 15 and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WKVHLPKGEGFSSG corresponding to amino acids 28 - 41 of HUMTREFACPEA-2_P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072050 PCT/IB2005/000433 890 2.An isolated polypeptide encoding for a tail of HUMTREFACPEA_2_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG in HUMTREFACPEA_2_PS. 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMTREFACPEA_2_PS also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates 15 whether the SNP is known or not; the presence of known SNPs in variant protein HIJMTREFACPEA-2_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid nmutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? 5 A->S No 5 A->T No 14 A->V Yes 20 Variant protein HUMTREFACPEA_2_P8 is encoded by the following transcript(s): HUMTREFACPEA_2_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTREFAC_PEA_2-T4 is shown in bold; this coding portion starts at position 278 and ends at position 400. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with 25 the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; WO 2005/072050 PCT/IB2005/000433 891 the presence of known SNPs in variant protein HUMTREFACPEA-2_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 233 A->G Yes 290 G->A No 290 G->T No 318 C -> T Yes 515 C -> A No 515 C->T No 566 C->T Yes 756 C -> A Yes 796 C->T No 1265 A->C No 1266 A->T No 5 As noted above, cluster HURMTREFAC features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 10 Segment cluster HUMTREFACPEA_2_node_0 according to the present invention is supported by 188 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFACPEA_2_T4 and HJMTREFACPEA_2_T5. Table 11 below describes the starting and ending position of this 15 segment on each transcript. Table 11 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 892 Transcript name Segment Segment starting position ending position HUMTREFACPEA_2_T4 1 359 HUMTREFACPEA_2_T5 1 359 Segment cluster HUJMTREFACPEA_2_node_9 according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HIUMTREFACPEA_2_T4 and HJMJ4TREFACPEA_2_T5. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMTREFACPEA_2_T4 681 1266 HUMTREFACPEA_2_T5 570 747 According to an optional embodiment of the present invention, short segments related to 10 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster HUMTREFACPEA_2_node_2 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This 15 segment can be found in the following transcript(s): HUIMTREFACPEA_2_T4. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMTREFACPEA_2_T4 360 470 WO 2005/072050 PCT/IB2005/000433 893 Segment cluster HUMTREFACPEA_2_node-3 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HLTMTREFACPEA_2_T4 and 5 HUMTREFACPEA_2_T5. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Seigment Segment starting position ending position HUMTREFAC PEA_2_T4 471 514 HUMTREFACPEA_2_T5 360 403 10 Segment cluster HUMTREFACPEA_2_node_4 according to the present invention is supported by 197 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HJMTREFACPEA_2_T4 and HUMTREFACPEA_2-T5. Table 15 below describes the starting and ending position of this segment on each transcript. 15 Table 15 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMTREFACPEA_2 T4 515 611 HUMTREFACPEA_2 T5 404 500 Segment cluster HLTMTREFACPEA_2_node_5 according to the present invention is supported by 187 libraries. The number of libraries was determined as previously described. 20 This segment can be found in the following transcript(s): HIUMTREFACPEA_2_T4 and WO 2005/072050 PCT/IB2005/000433 894 HUMTREFACPEA_2_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMTREFACPEA_2_T4 612 661 HUMTREFACPEA_2_T5 501 550 5 Segment cluster HUMTREFACPEA_2_node_8 according to the present invention can be found in the following transcript(s): HUMTREFACPEA_2_T4 and HIUMTREFACPEA_2_T5. Table 17 below describes the starting and ending position of this segment on each transcript. 10 Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position ifGMTREFACPEA_2_T4 662 680 HUMTREFACPEA 2_T5 551 569 Variant protein alignment to the previously known protein: 15 sequence name: TFF3_HUMAN Sequence documentation: Alignment of: HUMTREFACPEA_2_P8 x TFF3_HUMAN 20 Alignment segment 1/1: WO 2005/072050 PCT/IB2005/000433 895 Quality: 246.00 Escore: 0 Matching length: 27 Total 5 length: 27 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 10 Gaps: 0 Alignment: 1 MAARALCMLGLVLALLSSSSAEEYVGL 27 15 | | | | 1|1| 1 |1|| |||1| | | 1 MAARALCMLGLVLALLSSSSAEEYVGL 27 20 DESCRIPTION FOR CLUSTER HUMOSTRO Cluster HTMOSTRO features 3 transcript(s) and 30 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table I - Transcripts of interest Transcript Name Sequence ID No. HUMOSTROPEA 1_PEA_1_T14 519 HUMOSTROPEA_1_PEA_1_T16 520 HTMOSTROPEA_1_PEA__T30 521 25 WO 2005/072050 PCT/IB2005/000433 896 Table 2 - Segments of interest Segment Name Sequence ID) No. HUMOSTROPEA_1_PEA_1_node_0 522 HUMOSTROPEA_1 PEA_ Inode_10 523 HUMOSTROPEA_1_PEA_1_node_16 524 HUMOSTROPEA1 _PEA 1_node_23 525 HUMIOSTRO_PEA_1_PEA_1_node_31 526 HUMOSTROPEA_1 PEA_1 node_43 527 JMOSTROPEA__PEAInode_3 528 HLUMOSTROPEA 1_PEA_1_node_5 529 HUMOSTROPEA 1_PEA_1_node_7 HUON4STROPEA_1_PEA_1_node_8 531 -UMOSTROPEA_1_PEA_1_node_15 532 HUJMOSTROPEA 1_PEA_1_node-17 533 HJMOSTROPEA_1_PEA_1_node_20 534 HU-JMOSTROPEA_1_PEA_1_node_21 535 IUNOSTROPEA_1 PEAInode_22 536 HUMOSTROPEA1 _PEA_1_node_24 537 HrUMOSTROPEA1__PEA_1_node_26 538 HUMOSTROPEA_1.PEA_1_node_27 539 HUMOSTROPEA_1_PEA_1_node_28 540 HUMOSTROPEA_1_PEA_1_node_29 541 HUMJIOSTROPEA_1_PEA 1_node_30 542 HUMOSTROPEA_1_PEA_1_node_32 543 HUMOSTROPEA_1_PEA_1_node_34 544 HUMvIOSTROPEA_1_PEA_node_36 545 HLTMOSTROPEA 1 PEA 1_node_37 546 HUIVIOSTROPEA_1_PEA_1_node_38 547 -LUMOSTRO-PEA-1SPEAe1nodeq39 548 WO 2005/072050 PCT/IB2005/000433 897 HLTMOSTROPEA_1 PEA_1_node_40 549 IIUMOSTROPEA_1_PEA_1_node_41 550 HUMOSTROPEA_1_PEA_node_42 551 Table 3 - Proteins of interest Protein Name Sequence ID Corresponding Transcript(s) HUMOSTRO PEA 1_PEA_1 P21 553 HUMOSTROPEA_1_PEA_1_T14 HUMOSTRO PEA_1_PEA_1_P25 554 HUMOSTROPEA_1-PEA_1_T16 HUMOSTRO PEA1 _PEA_P30 555 H{UMOSTROPEA_1._PEA_1_T30 These sequences are variants of the known protein Osteopontin precursor (SwissProt 5 accession identifier OSTPHUMAN; known also according to the synonyms Bone sialoprotein 1; Urinary stone protein; Secreted phosphoprotein 1; SPP- 1; Nephropontin; Uropontin), SEQ ID NO: 552, referred to herein as the previously known protein. Protein Osteopontin precursor is known or believed to have the following function(s): Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. 10 Probably important to cell-matrix interaction;Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin- 12 and reducing production of interleukin- 10 and is essential in the pathway that leads to type I immunity (By similarity). The sequence for protein Osteopontin precursor is given at the end of the application, as "Osteopontin precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. 15 Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 301 R-> H (in dbSNP:4660). /FTId=VAR_014717. 188 D ->H 237 T->A 275 - 278 SHEF -> GNSL WO 2005/072050 PCT/IB2005/000433 898 Protein Osteopontin precursor localization is believed to be Secreted. The previously known protein also has the following indication(s) and/or potential 5 therapeutic use(s): Regeneration, bone. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Bone formation stimulant. A therapeutic role for a protein represented by 10 the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or tle public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Musculoskeletal. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: ossification; anti-apoptosis; inflammatory response; cell-matrix 15 adhesion; cell-cell signaling, which are annotation(s) related to Biological Process; defense/immunity protein; cytokine; integrin ligand; protein binding; growth factor; apoptosis inhibitor, which are annotation(s) related to Molecular Function; and extracellular matrix, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl 20 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HUMOSTRO can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 25 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 37 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 30 Overall, the following results were obtained as shown with regard to the histograms in Figure 37 and Table 5. This cluster is overexpressed (at least at a minimum level) in the WO 2005/072050 PCT/IB2005/000433 899 following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors, breast malignant tumors, ovarian carcinoma and skin malignancies. 5 Table 5 - Normal tissue distribution Name of Tissue Number renall 4 bladder 0 bone 897 brain 506 colon 69 epithelial 548 general 484 head and neck 50 kidney 5618 liver 4 lung 10 lymph nodes 75 breast 8 bone marrow 62 muscle 37 ovary 40 pancreas 845 prostate 48 skin 13 stomach 73 Thyroid 0 uterus 168 WO 2005/072050 PCT/IB2005/000433 900 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 adrenal 1.5e-01 2.le-01 2.0e-02 4.6 4.4e-02 3.6 bladder 1.2e-01 9.2e-02 5.7e-02 4.1 2.le-02 4.3 bone 4.9e-01 7.4e-01 4.le-06 0.6 5.4e-01 0.4 brain 6.6e-01 7.0e-01 3.2e-O1 0.6 1 0.4 colon 2.7e-01 4.0e-01 3.le-01 1.5 5.2e-01 1.1 epithelial 2.Oe-07 1.6e-03 9.8e-01 0.7 1 0.5 general 1.2e-06 1.2e-02 7.9e-01 0.8 1 0.6 head and neck 3.4e-01 5.0e-01 1 0.7 1 0.7 kidney 6.8e-0l 7e-0-01 1 0.2 1 0.1 liver 3.3e-01 2.5e-01 1 1.8 2.3e-01 2.6 lung 4.3e-04 4.6e-03 2.le-30 15.0 2.8e-27 23.5 lymph nodes 6.7e-01 8.7e-01 8.le-01 0.7 9.9e-01 0.3 breast 2.3e-01 3.0e-01 1.9e-04 6.2 4.le-03 4.3 bone marrow 7.5e-0l 7.8e-01 1 0.3 2.0e-02 1.2 muscle 4.0e-02 7.5e-02 .le-01 4.6 5.le-01 1.5 ovary 4.7e-02 8.4e-02 1.9e-05 5.4 8.3e-04 3.7 pancreas 5.Oe-02 3.3e-01 1 0.3 1 0.2 prostate 8.5e-01 9.Oe-01 89e-01 0.7 9.5e-01 0.6 skin 1.6e-01 1.6e-01 1.2e-10 12.6 5.2e-04 4.1 stomach 1.5e-01 6.3e-01 5.0e-01 1.2 9.4e-01 0.6 Thyroid 2.9e-01 2.9e-01 5.9e-02 2.0 5.9e-02 2.0 uterus 6.le-02 5.7e-01 1.le-01 1.3 .7.Oe-01 0.7 As noted above, cluster TMOSTRO features 3 transcriptss, which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Osteopontin precursor. A description of each variant protein according to the present invention is now 5 provided.

WO 2005/072050 PCT/IB2005/000433 901 Variant protein H-UMOSTROPEA-_1PEA-l_P21 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMOSTROPEA_1_PEA_1 T14. An alignment is given to the known protein (Osteopontin precursor) at the end of the application. One or more alignments to one or more previously 5 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMOSTROPEA_1_PEA_1_P21 and OSTP_IHUMAN: 1.An isolated chimeric polypeptide encoding for HUJMOSTROPEA_1PEA_P21, 10 comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ corresponding to amino acids 1 - 58 of OSTPHUMAN, which also corresponds to amino acids 1 - 58 of HUMOSTROPEA-_1PEALP21, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 15 preferably at least 95% homologous to a polypeptide having the sequence VFLNFS corresponding to amino acids 59 - 64 of HUMOSTROPEAIPEA-_P 2 1, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMOSTRO PEAIPEAiP21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least 20 about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VFLNFS in HUMOSTROPEA_1_PEA_1_P21. The location of the variant protein was determined according to results fiom a number of different software programs and analyses, including analyses from SignalP and other specialized 25 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure. Variant protein HUMOSTROPEA_1_PEA_1_P21 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their 30 position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein WO 2005/072050 PCT/IB2005/000433 902 HUMOSTRO-PEA_1_PEA_1_P21 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations §NP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 7 C->W No 31 Q -> R No 47 D->V Yes 49 S-> No 5 The glycosylation sites of variant protein HUNMOSTROPEA._1PEA_1_P21, as compared to the known protein Osteopontin precursor, are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). 10 Table 8 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 79 no 106 no Variant protein HUMOSTRO PEA_ 1PEA_1_P21 is encoded by the following transcript(s): HUMOSTROPEAIPEA_114, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMOSTROPEA_1_PEA_1_T14 is 15 shown in bold; this coding portion starts at position 199 and ends at position 390. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein WO 2005/072050 PCT/IB2005/000433 903 HUMOSTROPEA_1_PEA_-P21 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 A -> G Yes 154 T-> No 159 G ->T Yes 219 C ->G No 274 G No 290 A-> G No 338 A-> T Yes 343 T->C No 413 G -> C Yes 707 C -> T Yes 708 C->A Yes 715 A -> G Yes 730 A->C No 730 A -> G No 746 T->C Yes 767 C -> T No 779 G -> A Yes 866 -> G No 869 T-> No 889 -> A No 891 A -> C No 891 A->G No 905 T->C No 910 ->G No WO 2005/072050 PCT/IB2005/000433 904 910-> T No 997 A->G No 1026 G ->C No 1042 -> G No 1042 ->T No 1071 A-> No 1071 A->C No 1098 A-> No 1105 C -> T No 1124 -> G No 1135 G->A Yes 1136 T-> No 1136 T->G No 1173 A->C No 1173 A->G No 1179 A->G No 1214 C -> T Yes 1246 T-> No 1246 T->A No 1359 A -> No 1359 A->G No 1362 T-> No 1365 C -> T Yes 1366 G->A Yes 1408 A->C No 1418 A->C No 1433 A->C No 1456 A->C No 1524 T->A No 1524 T->C No WO 2005/072050 PCT/IB2005/000433 905 1547 A-> G Yes 1553 T-> No 1574 -> G No 1654 A->C Yes 1691 A -> G No 1703 A->C Yes 1755 A->C No 1764 T -> No Variant protein HUMOSTROPEA_1_PEA_1_P25 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMOSTROPEA_1_PEA_._T16. An alignment is given to the known protein (Osteopontin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between H-UMOSTROPEA_1 PEA_1_P25 and OSTP_HUMAN: 1.An isolated chimeric polypeptide encoding for HJMOSTROPEA-_1PEA_1_P25, comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1 - 31 of OSTPHUMAN, which also corresponds to amino acids 1 - 31 of 15 HUMOSTRO-PEA_1_PEAlP25, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence H corresponding to amino acids 32 - 32 of HUJMOSTROPEA_1_PEA_1_P25, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: WO 2005/072050 PCT/IB2005/000433 906 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMOSTROPEA_ 1_PEA__P25 also has the following non-silent 5 SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTROPEA_1_PEA_1_P25 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 7 C ->W No 31 Q->R No The glycosylation sites of variant protein HUMOSTROPEA-1_PEA_1_P25, as compared to the known protein Osteopontin precursor, are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column 15 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 11 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 79 no 106 no Variant protein HUMOSTRO-PEA_1_PEA_1_P25 is encoded by the following 20 transcript(s): HUMOSTROPEAIPEA_1_T16, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript IJMOSTROPEAIPEA_1_Ti6 is WO 2005/072050 PCT/IB2005/000433 907 shown in bold; this coding portion starts at position 199 and ends at position 294. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 5 HUMOSTROPEA_1_PEA_1 P25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 A->G Yes 154 T-> No 159 G -> T Yes 219 C -> G No 274 -> G No 290 A-> G No 419 C -> T Yes 454 G->C Yes 527 A->T Yes 532 T->C No 630 C -> T Yes 631 C -> A Yes 638 A -> G Yes 653 A -> C No 653 A -> G No 669 T->C Yes 690 C -> T No 702 G -> A Yes 789 -> G No 792 T -> No WO 2005/072050 PCT/IB2005/000433 908 812 ->A No 814 A->C No 814 A->G No 828 T->C No 833 -> G No 833 -> T No 920 A->G No 949 G->C No 965 ->G No 965 -> T No 994 A-> No 994 A->C No 1021 A -> No 1028 C->T No 1047 -> G No 1058 G->A Yes 1059 T-> No 1059 T->G No 1096 A->C No 1096 A -> G No 1102 A -> G No 1137 C->T Yes 1169 T-> No 1169 T->A No 1282 A-> No 1282 A -> G No 1285 T-> No 1288 C -> T Yes 1289 G->A Yes 1331 A->C No WO 2005/072050 PCT/IB2005/000433 909 1341 A->C No 1356 A->C No 1379 A->C No 1447 T->A No 1447 T->C No 1470 A->G Yes 1476 T-> No 1497 -> G No 1577 A->C Yes 1614 A->G No 1626 A->C Yes 1678 A->C No 1687 T-> No Variant protein HIMOSTROPEA_1_PEA_1_P30 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMOSTROPEA_1_PEA_1_T30. An alignment is given to the known protein (Osteopontin precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HUMOSTROPEA_1_PEA_1_P30 and OSTP_-HUMAN: I.An isolated chimeric polypeptide encoding for HUMOSTROPEA_-PEA_1_P30, comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1 - 31 of OSTP_HUMAN, which also corresponds to amino acids 1 - 31 of 15 HUMOSTROPEA_1_PEA_1_P30, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSIFYVFI WO 2005/072050 PCT/IB2005/000433 910 corresponding to amino acids 32 - 39 of HUMOSTROPEA_1_PEA_1_P30, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMOSTROPEA_1_PEAlP30, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least 5 about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSIFYVFI in HUMOSTROPEA-_1PEA_1_P30. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMOSTROPEA_1_PEA_1_P30 also has the following non-silent 15 SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTROPEA-1_PEA_1_P30 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 7 C -> W No 31 Q -> R No The glycosylation sites of variant protein HUMOSTROPEA_1_PEA_1_P30, as compared to the known protein Osteopontin precursor, are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column 25 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

WO 2005/072050 PCT/IB2005/000433 911 Table 14 - Glycosylation site(s) Position(s) on known idno Present in variant protein? acid sequence 79 no 106 no Variant protein HUMOSTROPEA_1_PEA_1_P30 is encoded by the following transcript(s): HIUMOSTROPEA-1_PEA_1_T30, for which the sequence(s) is/are given at the 5 end of the application. The coding portion of transcript HUMOSTROPEA_1_PEA_1_T30 is shown in bold; this coding portion starts at position 199 and ends at position 315. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 10 HUMOSTRO-PEA_1_PEA__P30 sequence provides support for the deduced sequence of this variant protein according to tle present invention). Table 15 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 136 A->G Yes 154 T-> No 159 G -> T Yes 219 C -> G No 274 -> G No 290 A -> G No 15 As noted above, cluster H-UMOSTRO features 30 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are WO 2005/072050 PCT/IB2005/000433 912 of particular interest. A description of each segment according to the present invention is now provided. Segment cluster HUIJMOSTROPEA_1_PEA_1_node_0 according to the present 5 invention is supported by 333 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEAIPEA-1-T14, HUMOSTROPEA_1_PEA_1_T16 and HUMOSTROPEA_1_PEA_1_T30. Table 16 below describes the starting and ending position of this segment on each transcript. 10 Table 16 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA1_PEA_1_T14 1 184 HUMOSTRO-PEA_1_PEA_1_T16 1 184 HUMOSTROPEA I PEA-1-T30 1 184 Segment cluster HUMOSTRO PEAIPEA_1_node 10 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously 15 described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T16. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA1_PEA_1_16 292 480 20 WO 2005/072050 PCT/IB2005/000433 913 Segment cluster HUMOSTRO-PEA_1_PEA1 node_16 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14. Table 18 below describes the starting and ending position 5 of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTRO PEA_1_PEA_1_T14 373 638 Segment cluster HUMOSTRO PEA-1_PEA_1_node_23 according to the present 10 invention is supported by 334 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO-PEA-1-PEA_1_T14 and HUJMOSTROPEA__PEA_1_T16. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA_1APEA_1_T14 804 967 HUMOSTROPEA_1_PEA_1_T16 727 890 15 Segment cluster HJMOSTROPEA_1-PEA_1 node_31 according to the present invention is supported by 350 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): 20 HUMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1-PEA_1_T16. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 914 Transcript name Segment Segment starting position ending position HUMOSTROPEA_1_PEA_1 T14 1164 1393 HLUMOSTRO.PEA_1_PEA_1_T16 1087 1316 Segment cluster HUMOSTROPEAIPEA_1_node_43 according to the present invention is supported by 192 libraries. The number of libraries was determined as previously 5 described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14 and HUJMOSTROPEA_1_PEA_1_T16. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTRO PEA 1 PEA_1_T14 1810 1846 HUMOSTROPEA-_PEA lT16 1733 1769 According to an optional embodiment of the present invention, short segments related to 10 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster HUMOSTRO-PEAIPEA_1_node_3 according to the present invention is supported by 353 libraries. The number of libraries was determined as previously 15 described. This segment can be found in the following transcript(s): HUMOSTROPEA__PEA_1_T14, HUfMOSTROPEA1_PEAIT16 and HUMOSTROPEA_1_PEA_1_T30. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment Segment starting position ending position, WO 2005/072050 PCT/IB2005/000433 915 HUMOSTRO-PEA_1_PEA-l_14 185 210 HUMOSTROQPEA_1_PEA_1_T16 185 210 HUMOSTRO PEA_1_PEA_1_T30 185 210 Segment cluster HUMOSTROPEA-_PEA_1_node_5 according to the present invention is supported by 353 libraries. The number of libraries was determined as previously 5 described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_TI4, HUMOSTROPEA_1_PEA_1-T16 and HUMOSTROPEA_1_PEAIT30. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment Segment starting position ending position H-IUMOSTROPEA_1_PEA_1_14 211 252 HUMOSTROPEA-1 PEA_1_T16 211 252 HUMOSTRO-PEA_1_PEA_1T30 211 252 10 Segment cluster HUMOSTRO-PEA_._PEA-_node_7 according to the present invention is supported by 357 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): 15 HUMOSTROPEA_1-PEA_1_T14, HUIMOSTROPEA_1_PEA_1_116 and H-UMOSTROPEA_1_PEAlT30. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTRO PEA_1_PEA114 253 291 WO 2005/072050 PCT/IB2005/000433 916 HUMIOSTROPEA_1_PEA_1_T16 253 291 HUMOSTROPEA_1_PEA_-T30 253 291 Segment cluster HUMOSTROPEA__PEA_1-node_8 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously 5 described. This segment can be found in the following transcript(s): HUMOSTRO-PEA_1_PEA_1_T30. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment Segment starting position ending position HJMOSTROPEA_1 PEA-IT30 292 378 10 Segment cluster HUMOSTROPEA 1 PEA_1_node_15 according to the present invention is supported by 366 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUJMOSTROPEA_1_PEA-_T14 and HUMOSTRO-PEA_1_PEA-lT16. Table 26 below 15 describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position IUMOSTRO.PEA_1_PEAI_T14 292 372 OSTROPEA_1_PEA_ lT16 481 561 Segment cluster HUMOSTRO-PEAIPEAInode 17 according to the present 20 invention is supported by 261 libraries. The number of libraries was determined as previously WO 2005/072050 PCT/IB2005/000433 917 described. This segment can be found in the following transcript(s): HUMOSTROPEA_1 PEA_1_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTRO-PEA_1_PEA_1_T14 639 680 HUMOSTRO-PEA_1_PEA_1_T16 562 603 5 Segment cluster HUMOSTROPEA_1_PEA_1_node_20 according to the present invention can be found in the following transcript(s): HUMOSTRO-PEA_1_PEA_1_T14 and HUMOSTRO-PEA_1_PEA_1_T16. Table 28 below describes the starting and ending position 10 of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEAI 1PEA_1_T14 681 688 HUMOSTROPEA_1 PEA_1_T16 604 611 Segment cluster HUIMOSTROPEA 1 PEA_1_node_21 according to the present 15 invention is supported by 315 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1-T16. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 918 Transcript name Segment Segment starting position ending position HITJMOSTROPEA_1_PEA_1_T14 689 738 HUMOSTROPEA1_PEA_1_T16 612 661 Segment cluster HUMOSTROPEA-_PEA_1 node_22 according to the present invention is supported by 322 libraries. The number of libraries was determined as previously 5 described. This segment can be found in the following transcript(s): H-UMOSTROPEA_1-PEA_1_T14 and HIJMOSTROPEA_1_PEA-1_T16. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segment Segment starting position ending position IUMOSTROPEA-1 PEA_1_T14 739 803 H{UMOSTRO-PEA_1_PEA_1_T16 662 726 10 Segment cluster HUMOSTRO-PEA_1_PEA 1 node_24 according to the present invention is supported by 270 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14 and HUMOSTRO PEA_1_PEAl_T16. Table 31 below 15 describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA_1-PEA_1_T14 968 1004 HUMOSTROPEA_1 PEA_1-T16 891 927 WO 2005/072050 PCT/IB2005/000433 919 Segment cluster HUMOSTROPEA_1_PEAinode_26 according to the present invention can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14 and HIUMOSTROPEAIPEA1_T16. Table 32 below describes the starting and ending position 5 of this segment on each transcript. Table 32 - Segment location on transcripts SegmentSemn Transcript name egetSegment starting position ending position HUMOSTROPEA_1_PEA1_T14 1005 1022 HUMOSTRO PEA 1_PEA_1_T16 928 945 Segment cluster HUMOSTROPEA_1_PEA_1_node_27 according to the present 10 invention is supported by 260 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO-PEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment Segment starting position ending position HMOSTROPEA_1_PEA_1_T14 1023 1048 HUMOSTRO-PEA_1_PEA 1_T16 946 971 15 Segment cluster HUJMOSTROPEA__PEA_ I node_28 according to the present invention is supported by 273 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): 20 HUMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1-T16. Table 34 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 920 Table 34 - Segment location on transcripts Transcript name Segment Segment starting position ending position IUMOSTROQPEA_1_PEA_1_T14 1049 1100 HUMOSTROPEA_1 PEA _T16 972 1023 Segment cluster HUMOSTROPEA_1_PEA- Inode_29 according to the present 5 invention is supported by 272 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEAI_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcrip t name Segment Segment starting position ending position HUMOSTROPEA 1_PEA_1_T14 1101 1151 HUMOSTROPEA-1_PEA_1 T16 1024 1074 10 Segment cluster HUMOSTRO-PEA_1_PEA_1_node_30 according to the present invention can be found in the following transcript(s):HUMJIvIOSTROPEA_1_PEA_1._T14 and H{UMOSTROPEA_1_PEA_1_T16. Table 36 below describes the starting and ending position 15 of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment Segment starting position ending position iUMOSTROPEA_1_PEA_1_T14 1152 1163 HUMOSTROPEA_1_PEA 1_T16 1075 1086 WO 2005/072050 PCT/IB2005/000433 921 Segment cluster HUMOSTROPEA_1_PEA-l_node_32 according to the present invention is supported by 293 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): 5 HUMOSTROPEA-1_PEA_1_T14 and HUMOSTROPEA_1_PEA-1_T16. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcrip t name Segment Segment starting position ending position HUMOSTRO-PEA1 PEA_1_T14 1394 1427 LIlMOSTRO PEA 1 PEA 1 T16 1317 1350 10 Segment cluster HUMOSTROPEA 1_PEA_1_node_34 according to the present invention is supported by 301 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROcPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 38 below describes the starting and ending position of this segment on each transcript. 15 Table 38 - Segment location on transcripts Transcript name Segment Segment starting position ending position I MOSTROPEA_1_PEA_1 T14 1428 1468 HIUMOSTROPEA_1_PEA_1_T16 1351 1391 Segment cluster HJMOSTROPEA1 PEA_1_node_36 according to the present invention is supported by 292 libraries. The number of libraries was determined as previously 20 described. This segment can be found in the following transcript(s): WO 2005/072050 PCT/IB2005/000433 922 HUMOSTROPEA_1_PEA_1-T14 and HUMOSTROPEA 1_PEAIT16. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting positionposition s ending position HJJMOSTROPEA 1_PEA_1_T14 1469 1504 HUMOSTROPEA_1 PEA 1_T16 1392 1427 5 Segment cluster LUMOSTRO-PEAIPEA-1 node_37 according to the present invention is supported by 295 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO PEA_1_PEA_1_T14 and HLUMOSTROPEA_1_PEA_1_T16. Table 40 below 10 describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA_1_PEA 1_T14 1505 1623 HUJMOSTROPEA_1JPEA1 _T16 1428 1546 Segment cluster HUMOSTROPEAI_PEA_1_node_38 according to the present 15 invention can be found in the following transcript(s): -UIMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA-1 T16. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072050 PCT/IB2005/000433 923 HUMOSTROPEA_1_PEA_1_T14 1624 1634 I{IUMOSTROPEA_1_PEA-1_T16 1547 1557 Segment cluster HUIIOSTRO-PEA_1_PEA_1_node_39 according to the present invention is supported by 268 libraries. The number of libraries was determined as previously 5 described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 42 below describes the starting and ending position of this segment on each transcript. Table 42 - Segment location on transcripts Transcript name Segment Segment starting position ending position HIUMOSTROPEA_1 PEA- _T14 1635 1725 HUMOSTROQPEA1 _PEA_1_T16 1558 1648 10 Segment cluster HUMOSTROPEA__PEA_1_node_40 according to the present invention can be found in the following transcript(s): HUJMOSTROPEA_1_PEA_1_T14 and HUMOSTROPEA_1_PEA_1_T16. Table 43 below describes the starting and ending position of this segment on each transcript. 15 Table 43 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA1 _PEA_1_T14 1726 1743 HUMOSTROPEA_1 PEAI_T16 1649 1666 Segment cluster HIUMOSTROPEA_1_PEA_1_node41 according to the present invention can be found in the following transcript(s): HUTNMOSTRO-PEA-_1PEA_1_T14 and WO 2005/072050 PCT/IB2005/000433 924 HUMOSTROPEA_1_PEA_1_T16. Table 44 below describes the starting and ending position of this segment on each transcript Table 44 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMOSTROPEA_1_PEA_1 T14 1744 1749 HUMOSTROPEA_1_PEA_1_T16 1667 1672 5 Segment cluster HJMOSTROPEA_1_PEA_1_node_42 according to the present invention is supported by 224 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTROPEA_1_PEAI_T14 and HUIMOSTROPEA_1_PEA_1_T16. Table 45 below 10 describes the starting and ending position of this segment on each transcript. Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HIMOSTROPEA1 PEA_1 T14 1750 1809 IUMOSTRO PEA_1_PEA_1_T16 1673 1732 15 Variant protein alignment to the previously known protein: Sequence name: OSTPHUMAN Sequence documentation: 20 Alignment of: HUMOSTROPEA_1_PEA_1_P21 x OSTPHUMAN WO 2005/072050 PCT/IB2005/000433 925 Alignment segment 1/1: Quality: 578.00 5 Escore: 0 Matching length: 58 Total length: 58 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQ 50 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQ 50 20 51 KQNLLAPQ 58 51 KQNLLAPQ 58 25 Sequence name: OSTP_HUMAN 30 Sequence documentation: WO 2005/072050 PCT/IB2005/000433 926 Alignment of: HUMOSTROPEA_1_PEA_1_P25 x OSTPHUMAN Alignment segment 1/1: 5 Quality: 301.00 Escore: 0 Matching length: 31 Total length: 31 10 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31 20 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31 25 Sequence name: OSTPHUMAN Sequence documentation: 30 Alignment of: HUMOSTROPEA 1_PEA 1 P30 x OSTPHUMAN WO 2005/072050 PCT/IB2005/000433 927 Alignment segment 1/1: Quality: 301.00 5 Escore: 0 Matching length: 31 Total length: 31 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31 1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31 20 DESCRIPTION FOR CLUSTER Ri 1723 Cluster RI 1723 features 6 transcript(s) and 26 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 25 Table 1 - Transcripts of interest Transcript Name Sequence ID No. RI 1723_PEA_1_TI 5 556 R11723_PEA_1_T17 557 RI 1723_PEAI_T19 558 RI 1723_PEAlT20 559 WO 2005/072050 PCT/IB2005/000433 928 R11723_PEA_1_T5 560 R11723_PEAIT6 561 Table 2 - Segments of interest Segment Name Sequence ID No. RI1723_PEA_1_node_13 562 R1 1723_PEA 1 node 16 563 R11723_PEA 1 node 19 564 R 11723_PEA_1 node_2 565 RI 1723_PEA_1_node_22 566 R11723_PEA_1_node_31 567 R1 1723_PEA_1 node_10 568 RI1723_PEA 1 node 11 569 RI 1723_PEA I node_15 570 RI1723_PEA_1_node-18 571 RI1723_PEA_1_node_20 572 R11723-PEA_1 node_21 573 RI 1723_PEA_1_node_23 574 RI 1723_PEA-_1node_24 575 Ri 1723_PEA_1-node_25 576 RI 1723_PEAInode_26 577 R11723_PEA_1_node_27 578 RI 1723_PEA_1-node_28 579 R11723_PEA_1_node_29 580 Ri 1723_PEA_1_node_3 581 RI 1723_PEA_1_node_30 582 R11723_PEA_1_node_4 583 R11723_PEA_1_node_5 584 R11723_PEA_1_node_6 585 WO 2005/072050 PCT/IB2005/000433 929 RI1723_PEA_1_node-7 586 R11723_PEA_1_node-8 587 Table 3 - Proteins of interest Protein Name Sequence I) No. R11723_PEA_1_P2 588 RI 1723_PEA_1_P6 589 RI 1723_PEA_1-P7 590 RI1723-PEA_1_P13 591 R11723_PEA 1P10 592 5 Cluster RI 1723 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of Figure 38 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to 10 the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 38 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors 15 from different tissues and kidney malignant tumors. Table 4 - Normal tissue distribution Name of Tissue Number adrenal 0 brain 30 epithelial 3 WO 2005/072050 PCT/IB2005/000433 930 general 17 head and neck 0 kidney 0 lung 0 breast 0 ovary 0 pancreas 10 skin 0 uterus 0 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue PI P2 SPi R3 SP2 R4 adrenal 4.2e-01 4.6e-01 4.6e-01 2.2 5.3e-01 1.9 brain 2.2e-01 2.0e-01 1.2e-02 2.8 5.0e-02 2.0 epithelial 3.0e-05 6.3e-05 l.8e-05 6.3 3.4e-06 6.4 general 7.2e-03 4.0e-02 1.3e-04 2.1 1.le-03 1.7 head and neck 1 5.0e-01 1 1.0 7.5e-01 1.3 kidney 1.5e-01 2.4e-01 4.4e-03 5.4 2.8e-02 3.6 lung 1.2e-01 1.6e-01 1 1.6 1 1.3 breast 5.9e-01 4.4e-01 1 1.1 6.8e-01 1.5 ovary 1.6e-02 1.3e-02 1.Oe-01 3.8 7.Oe-02 3.5 pancreas . 5.5e-01 2.0e-01 3.9e-01 1.9 1.4e-01 2.7 skin 1 4.4e-01 1 1.0 1.9e-02 2.1 uterus 1.5e-02 5.4e-02 1.9e-01 3.1 1.4e-01 2.5 As noted above, cluster RI 1723 features 6 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. 5 Variant protein RI 1723_PEAlP2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Ri 1723_PEA_1_T6. The location of the variant protein was determined according to results WO 2005/072050 PCT/IB2005/000433 931 from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither 5 trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein RI 1723_PEA_1_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA-1_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 107 H ->P Yes 70 G-> No 70 G->C No 15 Variant protein RI 1723_PEA_1_P2 is encoded by the following transcript(s): RI 1723_PEAIT6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R1 1723_PEA_ 1 _T6 is shown in bold; this coding portion starts at position 1716 and ends at position 2051. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 20 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Rl 1723_PEA-lP2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs WO 2005/072050 PCT/IB2005/000433 932 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1231 C -> T Yes 1278 G ->C Yes 1923 G-> No 1923 G->T No 2035 A -> C Yes 2048 A -> C No 2057 A -> G Yes Variant protein RI 1723_PEA_lP6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 R1 1723-PEA_1_T15. One or more alignments to one or more previously published protein sequences are given at the end of the application A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between R1 1723_PEA_1_P6 and Q8IXMO (SEQ ID NO:885): 10 1.An isolated chimeric polypeptide encoding for RI 1723_PEA_1-P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 15 MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR corresponding to amino acids 1 - 110 of RI 1723_PEA_1_P6, and a second amino acid sequence being at least 90 % homologous to MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHV RPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ 20 corresponding to amino acids I - 112 of Q8IXMO, which also corresponds to amino acids 111 - WO 2005/072050 PCT/IB2005/000433 933 222 of Ri 1723_PEA-LP6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of RI 1723_PEA-lP6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR of Ri 1723_PEA_1_P6. 10 Comparison report between RI 1723_PEA_1_P6 and Q96AC2 (SEQ ID NO:886): 1.An isolated chimeric polypeptide encoding for Ri 1723_PEA-lP6, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 15 MEQSAGIIMYRKSCASSAACLIASAG corresponding to amino acids 1 - 83 of Q96AC2, which also corresponds to amino acids 1 - 83 of RI 1723_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL 20 RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEALP6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA-lP6, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ 30 CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723_PEA_1_P6.

WO 2005/072050 PCT/IB2005/000433 934 Comparison report between RI 1723_PEA_1_P6 and Q8N2G4 (SEQ ID NO:887): I .An isolated chimeric polypeptide encoding for RI 1723_PEAlP6, comprising a first amino acid sequence being at least 90 % homologous to 5 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 1 - 83 of Q8N2G4, which also corresponds to amino acids 1 - 83 of Ri 1723_PEAL-P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVREVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1-P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of RI 1723_PEA_l-P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL 20 RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723_PEA-1_P6. Comparison report between RI 1723_PEA__P6 and BAC85518 (SEQ ID NO:888): 1.An isolated chimeric polypeptide encoding for RI 1723_PEAlP6, comprising a first 25 amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 24 - 106 of BAC855 Is, which also corresponds to amino acids 1 - 83 of RI 1723_PEA_-JP6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 30 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072050 PCT/IB2005/000433 935 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in 5 a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA_1 P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723-PEA_1_P6. The location of the variant protein was determined according to results from a number of 15 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 20 Variant protein Ri 1723_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the 25 present invention). Table 8 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence ISO G-> No 180 G ->C No WO 2005/072050 PCT/IB2005/000433 936 217 H->P Yes Variant protein RI 1723-PEA_-P6 is encoded by the following transcript(s): RI 1723_PEA-1_T15, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Ri 1723_PEA_ _T15 is shown in bold; this coding portion starts at 5 position 434 and ends at position 1099. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA-_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 971 G -> No 971 G -> T No 1083 A -> C Yes 1096 A -> C No 1105 A -> G Yes Variant protein RI 1723_PEA_1_P7 according to the present invention has an amino acid sequence as given at tle end of the application; it is encoded by transcript(s) 15 RI 1723_PEA_1_T17. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between RI 1723_PEA_1_P7 and Q96AC2: 20 I.An isolated chimeric polypeptide encoding for R1 1723-PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to

MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV

WO 2005/072050 PCT/IB2005/000433 937 MEQSAG corresponding to amino acids 1 - 64 of Q96AC2, which also corresponds to amino acids 1 - 64 of RI 1723_PEALP7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Ri 1723_PEA_LP7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA-lP7. Comparison report between RI 1723_PEA_1_P7 and Q8N2G4: I.An isolated chimeric polypeptide encoding for Ri 1723_PEA_ 1 P7, comprising a first amino acid sequence being at least 90 % homologous to 15 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1 - 64 of Q8N2G4, which also corresponds to amino acids 1 - 64 of R11723_PEA_1_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in Ri 1723-PEA_1_P7. Comparison report between RI 1723_PEAlP7 and BAC85273: I.An isolated chimeric polypeptide encoding for RI 1723_PEA_1 P7, comprising a first 30 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more WO 2005/072050 PCT/IB2005/000433 938 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of Rl 1723_PEA_1_P7, second amino acid sequence being at least 90 % homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFlVNCTVNVQDMCQKEVMEQSAG 5 corresponding to amino acids 22 - 80 of BAC85273, which also corresponds to amino acids 6 64 of RI 1723_PEA-lP7, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of 10 R I1723_PEA_lP7, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of RI 1723_PEA-_ P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence MWVLG of RI1723_PEA_ 1_P7. 3.An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA__P7. 20 Comparison report between RI 1723_PEA_1_P7 and BAC85518: 1.An isolated chimeric polypeptide encoding for Ri 1723_PEA-lP7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 25 MEQSAG corresponding to amino acids 24 - 87 of BAC85518, which also corresponds to amino acids 1 - 64 of RI 1723_PEA_1_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of WO 2005/072050 PCT/IB2005/000433 939 Ri 1723_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Ri 1723_PEALP7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEAl-P7. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein RI 1723_PEA_1_P7 also has the following non-silent SNPs (Single 15 Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA-1-P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 10 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 67 C ->S Yes Variant protein RI 1723_PEAlP7 is encoded by the following transcript(s): RI 1723_PEA_1_T17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Ri 1723_PEA_1_T17 is shown in bold; this coding portion starts at 25 position 434 and ends at position 712. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of WO 2005/072050 PCT/IB2005/000433 940 known SNPs in variant protein RI 1723_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 625 G ->T Yes 633 G ->C Yes 1303 C ->T Yes 5 Variant protein RI 1723_PEA_1-P13 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Ri 1723_PEA-_T19. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 10 variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Ri 1723_PEA 1 P13 and Q96AC2: l.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P13, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 15 MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of R11723_PEA_1_P13, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT corresponding to amino acids 64 - 84 of 20 Ri 1723_PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA-1_P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence DTKRTNTLLFEMRHFAKQLTT in RI 1723_PEA_1_P13.

WO 2005/072050 PCT/IB2005/000433 941 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein RI 1723_PEA_1_P13 is encoded by the following transcript(s): 10 Ri 1723_PEA_1_T19 and RI 1723_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript RI 1723-PEA_-T19 is shown in bold; this coding portion starts at position 434 and ends at position 685. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is 15 known or not; the presence of known SNPs in variant protein RI 1723_PEA-1_P13 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 778 G -> T Yes 786 G -> C Yes 1456 C -> T Yes 20 Variant protein RI 1723_PEA_1_PlO according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) RI 1723-PEA_1_T20. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 25 variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 942 Comparison report between RI 1723_PEA-_PlO and Q96AC2: 1.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P1O, comprising a first amino acid sequence being at least 90 % homologous to 5 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of RI 1723_PEALP1O, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of Ri 1723_PEA_1_P10, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of R1 1723_PEA_1_Pl0, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PlO. Comparison report between RI 1723_PEA_1_PlO and QSN2G4: 1.An isolated chimeric polypeptide encoding for R11723_PEA_-_Pl0, comprising a first 20 amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q8N2G4, which also corresponds to amino acids 1 - 63 of Ri 1723_PEALP10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 25 preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_1-P10, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA_1_Pl0, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072050 PCT/IB2005/000433 943 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PlO. Comparison report between RI 1723_PEA_1_PlO and BAC85273: 5 1.An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_P10, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of Ri 1723_PEAI_P10, second amino acid sequence being at least 90 % homologous to 10 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 22 - 79 of BAC85273, which also corresponds to amino acids 6 63 of RI 1723_PEA_1_PlO, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_-_P10, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of RI 1723_PEA_1_Pl0, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 20 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG of R11723_PEA_1_PlO. 3.An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in Ri 1723_PEA_1_PlO. Comparison report between R11723_PEA-1_P10 and BAC85518: 1.An isolated chimeric polypeptide encoding for Ri 1723_PEALP 10, comprising a first amino acid sequence being at least 90 % homologous to 30 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV WO 2005/072050 PCT/IB2005/000433 944 MEQSA corresponding to amino acids 24 - 86 of BAC85518, which also corresponds to amino acids 1 - 63 of R 11723-PEA-LP 10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_iPlO, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723-PEA-1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in Ri 1723_PEA_1_P10. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows withregard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans- membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein RI 1723_PEA_1_PlO also has the following non-silent SNPs (Single 20 Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA_1-PlO sequence provides support for the deduced sequence of this variant protein according to the present invention). 25 Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 66 V->F Yes WO 2005/072050 PCT/IB2005/000433 945 Variant protein RI 1723_PEA-_P1O is encoded by the following transcript(s): RI 1723-PEA_lT20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Ri 1723_PEA_1_T20 is shown in bold; this coding portion starts at position 434 and ends at position 703. The transcript also has the following SNPs as listed in 5 Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Ri 1723-PEA_1_P10 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 629 G -> T Yes 637 G ->C Yes 1307 C -> T Yes 10 As noted above, cluster RI 1723 features 26 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 15 Segment cluster RI 1723-PEA-1_node_13 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T19, RI 1723_PEA_1_T5 and Ri 1723_PEA_1_T6. Table 15 below describes the starting and ending position of this segment 20 on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723-PEA_119 624 776 RI1723_PEA_1_T5 624 776 WO 2005/072050 PCT/IB2005/000433 946 RI 1723_PEA_1_T6 658 810 Segment cluster RI 1723_PEA_1_node_16 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): RI1723_PEA_1_T17, RI1723_PEA_1_T19 and Ri 1723_PEA_1-T20. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI 1723_PEA_1_T17 624 1367 R1723-PEA_1T 19 777 1520 RI1723_PEA_1_T20 628 1371 10 Segment cluster Ri 1723_PEAInode_19 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T5 and RI 1723_PEA_1-T6. Table 17 below describes the starting and ending position of this segment on each transcript. 15 Table 17 - Segment location on transcripts Transcript name Segment starting position, Segment ending position RI1723_PEAlT5 835 1008 RI1723_PEA_1_T6 869 1042 Segment cluster Ri 1723_PEA_1_node_2 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): RI 1723_PEA_LTI5, Ri 1723_PEA_1_T17, WO 2005/072050 PCT/IB2005/000433 947 Rl1723_PEA-l_T19, R 1723_PEAlT20, R 1723_PEA_1_T5 and RI 1723_PEA_1-T6. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position R1723_PEA_1_T15 1 309 RI1723_PEA_1 T17 1 309 R11723_PEA_1 T19 1 309 RI1723_PEA_1_T20 1 309 R11723_PEA_1_T5 1 309 R11723_PEA_1_T6 1 309 5 Segment cluster R1 1723_PEA-1_node_22 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Ri 1723_PEA-1_T5 and RI 1723_PEAIT6. Table 19 below describes the starting and ending position of this segment on each transcript. 10 Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position R _723-PEA__T5 1083 1569 R11723_PEAl-T6 1117 1603 Segment cluster RI 1723_PEA_1-node_31 according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): R11723-PEA_I_T15, R11723_PEAIT5 and RI 1723_PEA_1_T6. Table 20 below describes the starting and ending position of this segment on each transcript (it should be noted that these transcripts show alternative polyadenylation). Table 20 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 948 Transcript name Segment starting position segmentt ending position R1723_PEA_1_Ti5 1060 1295 Rl1723_PEA_1 T5 1978 2213 R1723_PEA 1 T6 2012 2247 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster RI 1723_PEA_1-node_10 according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Ri 1723_PEA-1_TI5, RI 1723_PEA_1_T17, R11723_PEA_-T19, R11723_PEA_1_T20, R11723-PEA I T5 and R1723_PEA_1_T6. Table 21 below describes the starting and ending position of this segment on each transcript. 10 Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T15 486 529 R11723_PEA_1_T17 486 529 R11723_PEA_1 T19 486 529 RI 1723-PEAlT20 486 529 R11723_PEAl-T5 486 529 R11723_PEA_1_T6 520 563 Segment cluster Ri 1723_PEA_1_node_11 according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): R11723_PEA_1_TI5, R11723-PEA_1-T17, R11723-PEA_1_T19, RI1723_PEA-lT20, R 1723_PEAlT5 and RI1723_PEA_1-T6. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts WO 2005/072050 PCT/IB2005/000433 949 Transcript name Segment starting position Segment ending position R11723_PEA_1Ti5 530 623 RI 1723_PEA 1_T17 530 623 R11723_PEA_1 T19 530 623 RI 1723_PEA_1_T20 530 623 RI 1723-PEA_1_T5 530 623 RI1723-PEA_1_T6 564 657 Segment cluster RI 1723-PEA-_node_15 according to the present invention can be found in the following transcript(s): RI 1723_PEA_1_T20. Table 23 below describes the starting 5 and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI 1723_PEA_1T20 624 627 Segment cluster RI 1723_PEA_1_node_18 according to the present invention is supported 10 by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T15, RI 1723-PEAIT5 and RI 1723_PEA_1_T6. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA_1_TI5 624 681 R11723_PEA_1_T5 777 834 RI1723_PEA_1_T6 811 868 15 WO 2005/072050 PCT/IB2005/000433 950 Segment cluster Ri 1723_PEA-_1node_20 according to the present invention can be found in the following transcript(s): Ri 1723_PEAIT5 and RI 1723_PEA_1_T6. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723-PEA_1_T5 1009 1019 Ri 1723_PEA__T6 1043 1053 5 Segment cluster RI 1723_PEA-_1node_21 according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Ri 1723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 10 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA_1T5 1020 1082 R11723_PEA__T6 1054 1116 Segment cluster R1 1723_PEA_1_node_23 according to the present invention is supported 15 by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T5 1570 1599 R11723_PEA_1_T6 1604 1633 20 WO 2005/072050 PCT/IB2005/000433 951 Segment cluster RI 1723_PEA_1_node_24 according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T15, RI 1723_PEA_1_T5 and R1 1723_PEA_1_T6. Table 28 below describes the starting and ending position of this segment 5 on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_Ti5 682 765 R11723-PEA_1_T5 1600 1683 RI1723_PEA1 _T6 1634 1717 Segment cluster RI 1723_PEA_1_node_25 according to the present invention is supported 10 by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_Ti5, RI 1723_PEA_1_T5 and Ri 1723_PEA_1-T6. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI 1723_PEA_1_TI5 766 791 R11723_PEAl-T5 1684 1709 R11723_PEA_I_T6 1718 1743 15 Segment cluster R1 1723_PEA_1_node_26 according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1-TI5, RI 1723_PEA_ 1_T5 and 20 Ri 1723_PEA_1_T6. Table 30 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 952 Table 30 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1 T15 792 904 RI1723_PEA_1_T5 1710 1822 RI1723_PEA-1-T6 1744 1856 Segment cluster RI 1723-PEA-1_node_27 according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T15, RI 1723_PEA-lT5 and 5 Ri 1723_PEA-lT6. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA _T1_ 5 905 986 R11723_PEA_1_T5 1823 1904 Rl1723_PEA_1_T6 1857 1938 10 Segment cluster RI 1723_PEA-_1node_28 according to the present invention can be found in the following transcript(s): RI 1723_PEA_1_Ti5, RI 1723_PEA_1_T5 and RI 1723_PEAlT6. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_115 987 - 1010 RI 1723_PEA_1_T5 1905 1928 Rl1723_PEA_1_T6 1939 1962 15 WO 2005/072050 PCT/IB2005/000433 953 Segment cluster RI 1723-PEA_1_node_29 according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1T15, RI 1723_PEA_1_T5 and Ri 1723-PEA_1_T6. Table 33 below describes the starting and ending position of this segment 5 on each transcript. Table 33 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA-1T15 1011 1038 R11723_PEA_1_T5 1929 1956 Rl1723_PEA_1_T6 1963 1990 Segment cluster RI 1723_PEA_1_node_3 according to the present invention can be found 10 in the following transcript(s): Ri 1723_PEA_1_Ti5, Ri 1723_PEA-1_T17, R11723_PEA_1_T19, Rl1723_PEA-lT20, R11723_PEA_1_T5 and R1723_PEA_T6. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI11723_PEA_1_TI5 310 319 RI1723_PEA1 _T17 310 319 R11723_PEA_1_T19 310 319 RI1723_PEA1 _T20 310 319 R11723_PEA__T5 310 319 RI1723_PEA_1_T6 310 319 15 Segment cluster RI 1723_PEA_1_node_30 according to the present invention can be found in the following transcript(s): RI 1723-PEA_1_Ti5, RI 1723_PEA_1_T5 and WO 2005/072050 PCT/IB2005/000433 954 RI 1723_PEA__T6. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA_1_TI5 1039 1059 R11723_PEAI _T5 1957 1977 RI1723_PEA__T6 1991 2011 5 Segment cluster RI 1723_PEA-_1node_4 according to the present invention is supported by 25 libraries. The number of libraries wNas determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1LT15, R11723_PEA_1_T17, RI 1723_PEA_1-T19, R11723_PEA-lT20, RI1723_PEA_1_T5 and Rll723_PEA_1_T6. 10 Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment starting position Segrhent ending position R11723_PEA I T15 320 371 R11723_PEA 1 T17 320 371 RI 1723_PEA 1 T19 320 371 RI 1723_PEA_1_T20 320 371 RI1723_PEA_1_TS 320 371 RI1723_PEAIT6 320 371 Segment cluster Ri 1723_PEA_1_node_5 according to the present invention is supported 15 by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_Ti5, R1 1723_PEA_1_T17, RI 1723_PEA-1_T19, R11723_PEA_1_T20, R 1723_PEAlT5 and R 1723_PEA_1_T6. Table 37 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 955 Table 37 - Segment location on transcripts Transcript name Segment starting position Segment ending position Rl1723_PEA_1_T15 372 414 R11723_PEA_1_T17 372 414 R11723_PEA_1_T19 372 414 R11723_PEA_1_T20 372 414 R11723_PEA_1_T5 372 414 R11723_PEA_1_T6 372 414 Segment cluster RI 1723-PEA_1_node_6 according to the present invention is supported 5 by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Ri 1723_PEA-1_TI5, RI 1723_PEA_1_T17, R11723_PEA-1.T19, R11723_PEAl-T20, RI1723-PEA_1T5 and Rll723_PEA-lT6. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T15 415 446 R11723_PEA_1 T17 415 446 R11723_PEA_1-T19 415 446 R11723_PEA_1T20 415 446 R11723_PEA-lT5 415 446 R11723_PEA_1_T6 415 446 10 Segment cluster RI 1723_PEAInode_7 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_TI5, RI 1723_PEA_1_T17, 15 RI 1723_PEA_1_T19, RI1723_PEA-lT20, RI1723_PEAIT5 and R1 1723_PEA_1_T6. Table 39 below describes the starting and ending position of this segment on each transcript.

WO 2005/072050 PCT/IB2005/000433 956 Table 39 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA 1_TI5 447 485 RI1723_PEA_1_T17 447 485 RI1723_PEA_1_T19 447 485 RI1723_PEA_1 T20 447 485 R11723_PEA_1_T5 447 485 R11723_PEA_1_T6 447 485 Segment cluster RI 1723_PEAInode-8 according to the present invention is supported 5 by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): RI 1723_PEA_1_T6. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment starting position Segment ending position RI1723_PEA_1_T6 486 519 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8IXMO 15 Sequence documentation: Alignment of: R11723_PEA_1_P6 x Q8IXMO Alignment segment 1/1: 20 WO 2005/072050 PCT/IB2005/000433 957 Quality: 1128.00 Escore: 0 Matching length: 112 Total length: 112 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 111 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDPAEVEKRLRE 160 15 1 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 50 161 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 210 51 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 100 20 211 RQRKEKHSMRTQ 222 111111111 101 RQRKEK-HSMRTQ 112 25 30 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q96AC2 WO 2005/072050 PCT/IB2005/000433 958 Sequence documentation: Alignment of: R11723_PEA_1_P6 x Q96AC2 5 Alignment segment 1/1: Quality: 835.00 Escore: 0 Matching length: 83 Total 10 length: 83 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 20 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 25 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 30 WO 2005/072050 PCT/IB2005/000433 959 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8N2G4 Sequence documentation: 5 Alignment of: R11723_PEA_1_P6 x Q8N2G4 Alignment segment 1/1: Quality: 835.00 10 Escore: 0 Matching length: 83 Total length: 83 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 - - 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 25 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 30 WO 2005/072050 PCT/IB2005/000433 960 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:BAC85518 5 Sequence documentation: Alignment of: R11723 PEA 1 P6 x BAC85518 .. Alignment segment 1/1: 10 Quality: 835.00 Escore: 0 Matching length: 83 Total length: 83 15 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 25 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 l i l l l l l l l l l l l l i l l l l l l l l l l l l l l l l i 74 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 106 30 WO 2005/072050 PCT/IB2005/000433 961 5 Sequence name: /tmp/VXjdFlzdBX/bexTxThOTh:Q96AC2 Sequence documentation: Alignment of: R11723_PEA_1_P7 x Q96AC2 10 Alignment segment 1/1: Quality: 654.00 Escore: 0 15 Matching length: 64 Total length: 64 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 20 Identity: 100.00 Gaps: 0 Alignment: 25 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSAG 64 3 0 | | | | | | | | | | | | | | 51 QDMCQKEVMEQSAG 64 WO 2005/072050 PCT/IB2005/000433 962 5 Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q8N2G4 Sequence documentation: 10 Alignment of: R11723_PEA_1_P7 x Q8N2G4 Alignment segment 1/1: 15 Quality: 654.00 Escore: 0 Matching length: 64 Total length: 64 Matching Percent Similarity: 100.00 Matching Percent 20 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 30 51 QDMCQKEVMEQSAG 64 WO 2005/072050 PCT/IB2005/000433 963 51 QDMCQKEVMEQSAG 64 5 Sequence name: /tmp/VXjdFlzdBX/bexTxThOTh:BAC85273 10 Sequence documentation: Alignment of: R11723_PEA_1_P7 x BAC85273 15 Alignment segment 1/1: Quality: 600.00 Escore: 0 Matching length: 59 Total 20 length: 59 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 25 Gaps: 0 Alignment: 6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55 3 0 | | | | | | | | | | | | | | | | | | |1| | | I | | | | | | 1 | | | 22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71 WO 2005/072050 PCT/IB2005/000433 964 56 KEVMEQSAG 64 | | | | | | i | | 72 KEVMEQSAG 80 5 10 Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85518 Sequence documentation: 15 Alignment of: R11723 PEA 1 P7 x BAC85518 Alignment segment 1/1: Quality: 654.00 20 Escore: 0 Matching length: 64 Total length: 64 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 30 . - - 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 WO 2005/072050 PCT/IB2005/000433 965 | | | | | | I 11 1 I I i l 1 |1 1111 1| | | | | 11 I I I I|| || I I *I |I I | ||I 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73 51 QDMCQKEVMEQSAG 64 5 | | | | | |1 1 1 1 74 QDMCQKEVMEQSAG 87 10 Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q96AC2 15 Sequence documentation: Alignment of: R11723_PEA_1_PlO x Q96AC2 Alignment segment 1/1: 20 Quality: 645.00 Escore: 0 Matching length: 63 Total length: 63 25 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072050 PCT/IB2005/000433 966 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 || ||II lI | | | I 1 1 1 1 1 1 I||I11 l I I|| | 1 1||||||| 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 5 51 QDMCQKEVMEQSA 63 51 QDMCQKEVMEQSA 63 10 15 Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q8N2G4 Sequence documentation: Alignment of: R11723_PEA_1_PlO x Q8N2G4 20 Alignment segment 1/1: Quality: 645.00 Escore: 0 25 Matching length: 63 Total length: 63 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 30 Identity: 100.00 Gaps: 0 WO 2005/072050 PCT/IB2005/000433 967 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 5 1111l1l I | | 1 I l l 111 11||1|| | | | |1| | |1 1 ||| 1 |||11 15 5 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSA 63 |1||||||||||1 10 51 QDMCQKEVMEQSA 63 15 Sequence name: /tmp/OLMSexEmIh/pc7Z7XmlYR:BAC85 2 73 Sequence documentation: 20 Alignment of: R11723_PEA_1 PlO x BAC85273 Alignment segment 1/1: 25 Quality: 591.00 Escore: 0 Matching length: 58 Total length: 58 Matching Percent Similarity: 100.00 Matching Percent 30 Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 968 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55 lilllllllll lll ll llll lllllll ll lllllllllllllll 22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71 10 56 KEVMEQSA 63 72 KEVMEQSA 79 15 20 Sequence name: /tmp/OLMSexEmIh/pc7Z7XmlYR:BAC85518 Sequence documentation: Alignment of: R11723 PEA 1 PlO x BAC85518 . 25 Alignment segment 1/1: Quality: 645.00 Escore: 0 30 Matching length: 63 Total length: 63 WO 2005/072050 PCT/IB2005/000433 969 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity:, 100.00 5 Gaps: 0 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 10 | | | | | | | | | | | | |1 | | | | | | | | | | | | | | | | | | | | | | 1 | 1 | | ||1 1 | 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73 51 QDMCQKEVMEQSA 63 | | | | |I l l l l l 15 74 QDMCQKEVMEQSA 86 20 Alignment of: R11723_PEA_1_P13 x Q96AC2 Alignment segment 1/1: 25 Quality: 645.00 Escore: 0 Matching length: 63 Total length: 63 30 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 WO 2005/072050 PCT/IB2005/000433 970 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 10 51 QDMCQKEVMEQSA 63 Illlllllil1ll 51 QDMCQKEVMEQSA 63 15 Expression of R 11723 transcripts which are detectable by amplicon as depicted in sequence name R 11723 seg13 in normal and cancerous breast tissues Expression of transcripts detectable by or according to segl3, R 11723 segl3 amplicon(s) 20 and R1 1723 segl3F and RI 1723 segl3R primers was measured by real time PCR. It should be noted that the variants of this cluster are variants of the hypothetical protein PSECO181 (referred to herein as "PSEC"). In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon), HPRTI (GenBank Accession No. NM_000194; amplicon - IPRTl-amplicon), and SDHTA (GenBank Accession No. NM_004168; 25 amplicon - SDHA-amplicon), G6PD (GenBank Accession No. NM000402; G6PD amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, "Tissue samples in testing panel" 30 above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

WO 2005/072050 PCT/IB2005/000433 971 Figure 39 is a histogram showing over expression of the above- indicated transcripts in cancerous breast samples relative to the normal samples. As is evident from Figure 39, the expression of transcripts detectable by the above amplicon(s) in cancer samples was higher than in the non-cancerous samples (Sample Nos. 56 5 60, 63-67 Table 1, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 5 out of 28 adenocarcinoma samples. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non 10 limiting illustrative example only of a suitable primer pair: R 11723 segl3F forward primer; and RI 1723 segl3R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R 11723 segl3. 15 R 11723seg I 3F (SEQ ID NO:889)- ACACTAAAAGAACAAACACCTTGCTC R I1723seg13R (SEQ ID NO:890)- TCCTCAGAAGGCACATGAAAGA RI 1723seg13 amplicon (SEQ ID NO:891): ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAGCAGTTG ACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA 20 Expression ofR 11723 transcripts which are detectable by amplicon as depicted in sequence name RI 1723seg13 in different normal tissues 25 Expression of R11723 transcripts detectable by or according to RI1723seg13 amplicon and RI] 723seg13F, RI]723seg13R was measured by real time PCR. In parallel the expression of four housekeeping genes RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession 30 No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of WO 2005/072050 PCT/IB2005/000433 972 the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20 Table 2 "Tissue samples in normal panel" above), to obtain a value of relative expression of each sample relative to median of the ovary samples. Primers and amplicon are as above. 5 The results are presented in Figure 40, demonstrating the expression of RI 1723 transcripts which are detectable by amplicon as depicted in sequence name RI 1723seg13 in different normal tissues. 10 Expression of Ri 1723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 junc11-18 in normal and cancerous breast tissues. Expression of transcripts detectable by or according to junc 11-18, R 11723 junc 11-18 amplicon(s) and R11723 juncll-18F and RI1723 juncll-1SR primers was measured by real 15 time PCR (this junction and hence the amplicon are found in the previous known protein, also termed the "wild type" or WT protein, for which the sequence is given herein; the protein is also called "PSEC"). Use of the known protein (WT protein) for detection of breast cancer, alone or in combination with one or more variants of this cluster and/or of any other cluster and/or of any known marker, also comprises an embodiment of the present invention. In parallel the 20 expression of four housekeeping genes PBGD (GenBank Accession No. BC019323; amplicon PBGD-amplicon), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1 amplicon), SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of 25 the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up regulation for each sample relative to median of the normal PM samples. Figure 41A is a histogram showing over expression of the above-indicated transcripts in 30 cancerous breast samples relative to the normal samples.

WO 2005/072050 PCT/IB2005/000433 973 As is evident from Figure 41A, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 5: "Tissue samples in breast cancer testing panel"). Notably an over expression of at least 5 fold was found in 5 out of 28 adenocarcinoma samples. 5 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: RI 1723 junc 1-ISF forward primer; and R 11723 junc 11-1 8R reverse primer. The present invention also preferably encompasses any amplicon obtained through the 10 use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R 11723 junc I1 18. R 11723junc II-18F (SEQ ID NO:892)- AGTGATGGAGCAAAGTGCCG R 1723 junci 1- 18R (SEQ ID NO:893) - CAGCAGCTGATGCAAACTGAG 15 R 11723 juncI1-18 (SEQ ID NO:894) AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCATCAGCGG CCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCAGGGAAACTGAACT CAGTTTGCATCAGCTGCTG 20 Expression of RI 1723 transcripts, which were detected by amplicon as depicted in the sequence name R 11723 junc I1-18 in different normal tissues. Expression of R11723 transcripts detectable by or according to Ri 723seg]3 amplicon and R11723 junc]1-18F, Ri] 723 junc]1-18R was measured by real time PCR (as described 25 above, this junction and hence the amplicon are found in the previous known protein, also termed the "wild type" or WT protein, for which the sequence is given herein; the protein is also called "PSEC"). In parallel the expression of four housekeeping genes RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), UJBC (GenBank Accession No. BC000449; amplicon 30 Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA amplicon) was measured similarly. For each RT sample, the expression of the above amplicon WO 2005/072050 PCT/IB2005/000433 974 was normalized to the geometric mean of the quantities of the houskeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2: Tissue samples in normal panel, above), to obtain a value of relative expression of each sample relative to median of the ovary samples. Figure 41B 5 shows the level of expression of this transcript. Primers and amplicon are as for the example above. The variant transcript expression pattern for this cluster is similar to the wild type transcript expression. However, in some cases (e.g. ovary cancer) over expression of the variant 10 seems to be higher (for example, with regard to RI 1723_PEAI_T5). DESCRIPTION FOR CLUSTER T46984 Cluster T46984 features 21 transcript(s) and 49 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end 15 of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name Sequence ID No. T46984-PEA-_T2 593 T46984_PEAIT3 594 T46984_PEA_1 T12 595 T46984_PEA_1 T13 596 T46984_PEA_1_T14 597 T46984-PEA_1_TI5 598 T46984_PEA_1 T19 599 T46984_PEAl-T23 600 T46984_PEAl-T27 601 T46984_PEA_1_T32 602 T46984-PEA-lT34 603 T46984_PEAl-T35 604 T46984_PEA_1_T40 605 WO 2005/072050 PCT/IB2005/000433 975 T46984_PEA_1_T42 606 T46984_PEA_1_T43 607 T46984_PEA_1_T46 608 T46984_PEAl-T47 609 T46984_PEA_1-T48 610 T46984_PEAlT51 611 T46984_PEAl-T52 612 T46984_PEA_1_T54 613 Table 2 - Segments of interest SegmentName Sequence ID No. T46984_PEA_1_node_2 614 T46984_PEA_1_node_4 615 T46984_PEA_1_node_6 616 T46984_PEA_1_node 12 617 T46984_PEA-_1node_14 618 T46984_PEA_1_node_25 619 T46984_PEA-_1node_29 620 T46984_PEA_1_node_34 621 T46984_PEA_1_node_46 622 T46984_PEA-_1node_47 623 T46984_PEA_1_node_52 624 T46984_PEA_1_node_65 625 T46984_PEA-_1node_69 626 T46984_PEA_1_node_75 627 T46984-PEA_1_node_86 628 T46984_PEA_1_node_9 629 T46984_PEA_1_node 13 630 T46984_PEA_1_node-19 631 WO 2005/072050 PCT/IB2005/000433 976 T46984_PEAInode_21 632 T46984_PEA_1_node_22 633 T46984_PEA_1-node_26 634 T46984_PEA-_1node_28 635 T46984_PEA_1_node_31 636 T46984_PEA__node_32 637 T46984_PEA lnode_38 638 T46984_PEA_1_node_39 639 T46984_PEA_1_node_40 640 T46984_PEA_1_node_42 641 T46984_PEA_1_node_43 642 T46984_PEA_1_node_48 643 T46984_PEA-_1node_49 644 T46984_PEA_1_node_50 645 T46984_PEA_1-node 51 646 T46984_PEA_1_node_53 647 T46984_PEA_1_node_54 648 T469S4_PEA-_1node_55 649 T46984_PEA_1_node_57 650 T46984_PEA_1_node_60 651 T46984_PEA_1_node_62 652 T46984-PEA_1_node_66 653 T46984_PEA-_1node_67 654 T46984_PEA_1_node_70 655 T46984_PEA_1_node_71 656 T46984_PEA_1_node_72 657 T46984_PEA_1_node_73 658 T46984_PEA_1_node_74 659 T46984_PEA_1_node-83 660 T46984_PEA_1_node_84 661 WO 2005/072050 PCT/IB2005/000433 977 T46984_PEA1node_85 662 Table 3 - Proteins of interest Protein Name Sequence ID No. Corresponding Transcript(s) T46984_PEA_1_P2 664 T46984_PEA_1_T2; T46984_PEA_1-T12; T46984_PEA_1-T23 T46984-PEA-1_P3 665 T46984_PEA_1_T3; T46984_PEA_1_T19 T46984_PEA_1-PIO 666 T46984_PEA_1_T13 T46984-PEA-1_P11 667 T46984-PEA-1_T14 T46984_PEA_1_P12 668 T46984_PEA_1-T15 T46984_PEAl-P21 669 T46984_PEA_1_T27 T46984_PEA_1_P27 670 T46984_PEA_lT34 T46984-PEA-1_P32 671 T46984-PEA_1_T40 T46984-PEA-1_P34 672 T46984_PEA_1_T42 T46984_PEA_1_P35 673 T46984_PEA-1_T43 T46984_PEAl-P38 674 T46984_PEA_1T47 T46984_PEA-lP39 675 T46984_PEA_1_T48 T46984-PEAlP45 676 T46984_PEA_lT32 T46984_PEA_1_P46 677 T46984_PEAlT35 These sequences are variants of the known protein Dolichyl-diphosphooligosaccharide- 5 protein glycosyltransferase 63 kDa subunit precursor (SwissProt accession identifier RIB2_HUMAN; known also according to the synonyms EC 2.4.1.119; Ribophorin II; RPN-II; RIBIIR), SEQ ID NO: 663, referred to herein as the previously known protein. Protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor is known or believed to have the following function(s): Essential subunit of N 10 oligosaccharyl transferase enzyme which catalyzes the transfer of a high mannose oligosaccharide from a lipid- linked oligosaccharide donor to an asparagine residue within an WO 2005/072050 PCT/IB2005/000433 978 Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. The sequence for protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor is given at the end of the application, as "Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor amino acid sequence". Known polymorphisms for 5 this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 197 V->L 201 F->C 260 A-> S 423 V->M Protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor localization is believed to be Type I membrane protein. Endoplasmic reticulum. 10 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein modification, which are annotation(s) related to Biological Process; oligosaccharyl transferase; dolichyl-diphosphooligosaccharide-protein glycosyltransferase; transferase, which are annotation(s) related to Molecular Function; and oligosaccharyl transferase complex; integral membrane protein, which are annotation(s) related 15 to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 20 Cluster T46984 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of Figure 42 refer to weighted expression of ESTs in WO 2005/072050 PCT/IB2005/000433 979 each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 5 Figure 42 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, ovarian carcinoma and pancreas carcinoma. Table 5 - Normal tissue distribution Name of Tissue Number adrenal 240 bladder 287 bone 592 brain 145 colon 157 epithelial 144 general 163 head and neck 50 kidney 139 liver 156 lung 155 lymph nodes 194 breast 105 bone marrow 62 muscle 62 ovary 0 pancreas 72 prostate 201 skin 91 WO 2005/072050 PCT/IB2005/000433 980 stomach 219 T cells 0 Thyroid 0 uterus 200 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 adrenal 6.3e-01 5.4e-01 6.2e-01 0.8 2.5e-01 1.0 bladder 5.4e-01 5.9e-01 3.0e-01 1.0 6.5e-01 0.7 bone 3.9e-01 3.7e-01 9.8e-01 0.4 9.9e-01 0.4 brain 3.3e-01 2.9e-01 1.4e-01 1.2 2.0e-01 1.0 colon 8.6e-02 5.9e-02 2.6e-01 1.3 2.le-03 1.4 epithelial 5.3e-05 6.2e-07 2.8e-08 1.9 3.4e-21 2.4 general 1.Oe-04 7.3e-08 9.3e-12 1.7 8.0e-33 2.0 head and neck 4.5e-01 5.4e-01 1 0.8 7.5e-01 0.9 kidney 6.6e-01 6.5e-01 3.2e-01 1.2 5.3e-02 1.5 liver 5.5e-01 5.6e-01 6.5e-01 1.0 1.2e-01 1.4 lung 3.0e-01 1.7e-01 1.5e-01 1.4 6.0e-02 1.4 lymph nodes 2.9e-01 5.5e-01 2.9e-01 0.8 4.3e-01 1.0 breast 2.4e-02 5.8e-03 3.7e-02 2.2 1.7e-04 2.7 bone marrow 7.le-01 7.5e-01 1 0.3 1.2e-02 1.8 muscle 5.0e-01 3.7e-01 4.7e-01 1.5 2.le-08 1.3 ovary 1.6e-02 7.0e-03 1.5e-02 6.1 4.8e-06 7.1 pancreas 1.4e-01 5.4e-02 2.2e-05 2.9 2.4e-07 3.9 prostate 3.4e-01 1.9e-01 2.2e-01 1.2 1.4e-01 1.3 skin 3.7e-01 1.5e-01 4.2e-02 2.4 1.le-04 1.9 stomach 6.le-01 1.4e-01 7.3e-01 0.4 6.le-02 1.6 T cells 1 6.7e-01 1 1.0 5.2e-01 1.8 Thyroid 4.8e-02 4.8e-02 2.0e-01 3.4 2.0e-01 3.4 WO 2005/072050 PCT/IB2005/000433 981 uterus 2.3e-01 1.3e-01 2.2e-02 1.5 5.0e-02 1.4 As noted above, cluster T46984 features 21 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Dolichyl diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor. A description of each variant protein according to the present invention is now provided. 5 Variant protein T46984_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA_1_T2. An alignment is given to the known protein (Dolichyl diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor) at the end of 10 the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T46984_PEA_1_P2 and RIB2_HJMAN: 1.An isolated chimeric polypeptide encoding for T46984_PEAlP2, comprising a first 15 amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLDHVGTEPSIKEDQVIQLMNA 20 IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1 - 498 of RIB2_HUMAN, 25 which also corresponds to amino acids 1 - 498 of T46984-PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VCA corresponding to amino acids 499 - 501 of T46984_PEA_1_P2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 30 WO 2005/072050 PCT/IB2005/000433 982 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. The glycosylation sites of variant protein T46984_PEA_1_P2, as compared to the known protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit 10 precursor, are described in Table 7 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 7 - Glycosylation site(s) Positions) on known amino Present in variant protein? Position in variant protein? acid sequence 106 yes 106 15 Variant protein T46984_PEA_1_P2 is encoded by the following transcript(s): T46984_PEA_1_T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984-PEA_1_T2 is shown in bold; this coding portion starts at position 316 and ends at position 1818. The transcript also has the following SNPs as listed in 20 Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEAlP2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence WO 2005/072050 PCT/IB2005/000433 983 28 G->C No 173 G-> C Yes 256 C->T Yes 274 G -> C Yes 325 C-> No 389 C -> G Yes 610 G-> A Yes 718 T-> No 724 C -> No 844 C -> T Yes 857 -> G No 885 C -> No 897 -> G No 1002 G -> A No 1048 A-> No 1048 A -> G No 1068 A -> C No 1076 G->A Yes 1187 A-> No 1187 A -> C No 1220 A -> G No 1220 A -> T No 1254 T-> G No 1291 A -> C No 1293 C -> G No 1303 G->A No 1376 G->T Yes 1588 A->C No 1618 T-> No 1618 T->C No WO 2005/072050 PCT/IB2005/000433 984 1660 T-> No 1693 A-> C No 1693 A->T No 2099 G->A Yes 2124 C -> G Yes 2124 C -> T Yes 2133 A->G Yes 2501 C -> T Yes 2617 G->T Yes 2683 C -> T Yes 2741 G->A Yes 2940 T-> No 3024 G-> A Yes 3158 C -> No 3158 C -> A No 3165 C -> No 3169 G-> No 3354 C -> A No 3374 T->C Yes 3468 C->T No 3501 A ->C No 3513 A->T No 3528 G->A Yes 3534 -> A No 3543 A -> G No 3568 T-> G No 3582 T->A No 3582 T->G No 3682 ->C No 3691 T-> No WO 2005/072050 PCT/IB2005/000433 985 3750 A-> C No Variant protein T46984_PEA_1_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T46984-PEA_1_T3. An alignment is given to the known protein (Dolichyl diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor) at the end of the application. One or more alignments to one or more previous ly published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T46984_PEA_1_P3 and RIB2_HUMAN: 1.An isolated chimeric polypeptide encoding for T469S4_PEAl-P3, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS 15 VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVISTEVGITNVDLSTVDKDQSIAPTTRVTYPAKAKGTFIADSHQNFAL 20 FFQLVDVNTGAELTPHQ corresponding to amino acids I - 433 of RIB2_HUMAN, which also corresponds to amino acids 1 - 433 of T46984_PEA_1_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ICHIWKLIFLP corresponding to amino acids 434 - 444 of T46984_PEA_1_P3, wherein said 25 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T46984_PEA_1_P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 30 sequence ICHIWKLIFLP in T46984_PEA_1_P3.

WO 2005/072050 PCT/IB2005/000433 986 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein T46984-PEA_1_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984-PEAlP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations SNP position(s) on amino acid Altermative amino acid(s) Previously known SNP? sequence 4 P-> No 25 P -> R Yes 99 G -> R Yes 135 F -> No 137 L-> No 190 R-> No 245 N -> No 245 N -> D No 251 E-> D No 254 S -> N Yes 291 Q-> No 291 Q ->P No 302 Q ->R No WO 2005/072050 PCT/IB2005/000433 987 302 Q ->L No 326 T->P No 330 D->N No 354 G->V Yes 425 T->P No The glycosylation sites of variant protein T46984_PEA_1.P3, as compared to the known protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor, are described in Table 10 (given according to their position(s) on the amino acid 5 sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 10 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 106 yes 106 10 Variant protein T46984_PEAl-P3 is encoded by the following transcript(s): T46984_PEA_1_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984-PEA_1_T3 is shown in bold; this coding portion starts at position 316 and ends at position 1647. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nuceotide sequence, with the alternative 15 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984-PEA-_lP3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known. SNP? sequence 2S G ->C No WO 2005/072050 PCT/IB2005/000433 988 173 G->C Yes 256 C ->T Yes 274 G-> C Yes 325 C -> No 389 C -> G Yes 610 G->A Yes 718 T-> No 724 C -> No 844 C -> T Yes 857 -> G No 885 C -> No 897 -> G No 1002 G->A No 1048 A -> No 1048 A->G No 1068 A -> C No 1076 G->A Yes 1187 A -> No 1187 A -> C No 1220 A -> G No 1220 A->T No 1254 T->G No 1291 A -> C No 1293 C -> G No 1303 G->A No 1376 G->T Yes 1588 A->C No 1784 C -> T Yes 1959 G->A Yes 2112 G -> A Yes WO 2005/072050 PCT/IB2005/000433 989 2137 C -> G Yes 2246 T -> No 2246 T->C No 2288 T-> No 2321 A -> C No 2321 A->T No 2552 C -> No 2552 C->A No 2559 C -> No 2563 G -> No 2748 C -> A No 2768 T->C Yes 2862 C->T No 2895 A->C No 2907 A->T No 2922 G->A Yes 2928 ->A No 2937 A->G No 2962 T-> G No 2976 T->A No 2976 T-> G No 3076 ->C No 3085 T-> No 3144 A -> C No Variant protein T46984_PEA_1_P10 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T46984_PEA_1_T13. An alignment is given to the known protein (Dolichyl diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor) at the end of WO 2005/072050 PCT/IB2005/000433 990 the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T46984_PEA_1_PIO and R1132_HUMAN: 5 1.An isolated chimeric polypeptide encoding for T46984-PEA_1_P1O, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI 10 VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPETTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS 15 ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1 - 498 of RIB2_HUMAN, which also corresponds to amino acids 1 - 498 of T46984-PEA-l_P1O, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LMDQK corresponding to amino acids 499 - 503 of T46984_PEALP1O, 20 wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T46984-PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence LMDQK in T46984_PEA_1_PO. The location of the variant protein was detennined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 30 secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072050 PCT/IB2005/000433 991 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein T46984_PEA_1_P1O also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA_1_P1O sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 4 P-> No 25 P ->R Yes 99 G ->R Yes 135 F-> No 137 L-> No 190 R-> No 245 N -> No 245 N -> D No 251 E-> D No 254 S -> N Yes 291 Q-> No 291 Q->P No 302 Q -> R No 302 Q -> L No 326 T->P No 330 D -> N No 354 G -> V Yes 425 T->P No WO 2005/072050 PCT/IB2005/000433 992 435 F-> No 435 F -> L No 449 F -> No 460 K -> * No 460 K->Q No The glycosylation sites of variant protein T46984_PEA_1_P10, as compared to the known protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor, are described in Table 13 (given according to their position(s) on the amino acid 5 sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 13 - Glycosylation sites) Posit ion(s) on. known amino Present in variant protein? Position. in variant protein? acid sequence 106 yes 106 10 Variant protein T46984_PEA_1_PIO is encoded by the following transcript(s): T46984_PEA_1_Ti3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA_1_T13 is shown in bold; this coding portion starts at position 316 and ends at position 1824. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative 15 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA_1P1O sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SATPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 2S G ->C No WO 2005/072050 PCT/IB2005/000433 993 173 G-> C Yes 256 C->T Yes 274 G-> C Yes 325 C-> No 389 C->G Yes 610 G-> A Yes 718 T-> No 724 C -> No 844 C -> T Yes 857 -> G No 885 C-> No 897 ->G No 1002 G->A No 1048 A-> No 1048 A -> G No 1068 A -> C No 1076 G->A Yes 1187 A-> No 1187 A -> C No 1220 A -> G No 1220 A -> T No 1254 T-> G No 1291 A -> C No 1293 C -> G No 1303 G->A No 1376 G->T Yes 1588 A->C No 1618 T-> No 1618 T->C No 1660 T-> No WO 2005/072050 PCT/IB2005/000433 994 1693 A-> C No 1693 A->T No 1845 T-> No 1983 C -> No 1983 C->A No 1990 C -> No 1994 G -> No 2179 C -> A No 2199 T->C Yes 2293 C->T No 2326 A -> C No 2338 A->T No 2353 G->A Yes 2359 -> A No 2368 A -> G No 2393 T-> G No 2407 T->A No 2407 T->G No 2507 -> C No 2516 T-> No 2575 A -> C No Variant protein T46984_PEA_1_P11 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T46984_PEA_1_T14. An alignment is given to the known protein (Dolichyl diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072050 PCT/IB2005/000433 995 Comparison report between T46984_PEA_1_P11 and RIB2_HUMAN: 1.An isolated chimeric polypeptide encoding for T46984_PEA_1PI 1, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL 5 GAQVPDAKIACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN 10 RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEK RPPTVVSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYWT QLNMFQTLKYLAILGSVTFLAGNRMLAQQAVKR corresponding to amino acids 1 - 628 of 15 RIB2_HUMAN, which also corresponds to amino acids 1 - 628 of T46984_PEA-1_P11. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 20 membrane. The protein localization is believed to be membrane because although both signal peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide. Variant protein T46984_PEA-1_P11 also has the following non-silent SNPs (Single 25 Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA_1_P11 sequence provides support for the deduced sequence of this variant protein according to the present invention). 30 Table 15 - Amino acid mutations WO 2005/072050 PCT/IB2005/000433 996 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 4 P-> No 25 P->R Yes 99 G -> R Yes 135 F -> No 137 L-> No 190 R-> No 245 N -> No 245 N -> D No 251 E->D No 254 S->N Yes 291 Q->P No 291 Q -> No 302 Q -> L No 302 Q -> R No 326 T->P No 330 D->N No 354 G -> V Yes 425 T->P No 435 F-> No 435 F->L No 449 F-> No 460 K->Q No 460 K -> * No 537 P->T No 537 P-> No 539 T-> No 540 V-> No WO 2005/072050 PCT/IB2005/000433 997 602 T->N No The glycosylation sites of variant protein T46984_PEA-1_P 1, as compared to the known protein Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor, are described in Table 16 (given according to their position(s) on the amino acid 5 sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 16 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 106 yes 106 10 Variant protein T46984_PEA_1_P11 is encoded by the following transcript(s): T46984_PEA_1_T14, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA-l_T14 is shown in bold; this coding portion starts at position 316 and ends at position 2199. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative 15 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA_1_P1 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 28 G->C No 173 G -> C Yes 256 C -> T Yes 274 G -> C Yes 325 C -> No WO 2005/072050 PCT/IB2005/000433 998 389 C ->G Yes 610 G-> A Yes 718 T-> No 724 C -> No 844 C -> T Yes 857 -> G No 885 C -> No 897 -> G No 1002 G -> A No 1048 A-> No 1048 A->G No 1068 A -> C No 1076 G->A Yes 1187 A -> No 1187 A->C No 1220 A->G No 1220 A->T No 1254 T->G No 1291 A->C No 1293 C -> G No 1303 G->A No 1376 G->T Yes 1588 A -> C No 1618 T-> No 1618 T->C No 1660 T-> No 1693 A->C No 1693 A->T No 1924 C -> No 1924 C -> A No WO 2005/072050 PCT/IB2005/000433 999 1931 C-> No 1935 G-> No 2120 C ->A No 2140 T->C Yes 2449 A -> Yes 2537 C -> T Yes 2614 C -> T Yes 2699 C -> T Yes 2857 G->A Yes 2879 A-> G Yes 3078 A-> G Yes 3354 G -> A Yes Variant protein T46984_PEA_1_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA_1_TI5. An alignment is given to the known protein (Dolichyl 5 diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T46984_PEA_1_P12 and RIB2_-HUMAN: 10 1.An isolated chimeric polypeptide encoding for T46984_PEA_1_P12, comprising a first amino acid sequence being at least 90 % homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI 15 VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMN corresponding to amino acids 1 - 338 of RIB2_HUMAN, which also corresponds to amino acids 1 - 338 of

Claims

1. An isolated polynucleotide comprising a polynucleotide having a sequence selected from the group consisting of: RI 1723_PEA_1_T15, RI 1723_PEA-_T17, R11723_PEA-1_T19, R11723_PEAlT20, R11723_PEA_1_T5, or R11723_PEA_1_T6.

2. An isolated polynucleotide comprising a node having a sequence selected from the group consisting of: RI 1723_PEA_1_node_13, RI 1723_PEA_1-node_16, R11723_PEA_1_node_19, R11723_PEAInode_2, R11723_PEA_1_node_22, R11723_PEA1_node3 1, R11723_PEAInode_10, R11723_PEA_1_node_11, R11723-PEA_1_node-15, R11723_PEA_1_node_18, R11723_PEA_1_node_20, R11723_PEA_1_node_21, R11723-PEAI1node 23, R11723_PEA__node_24, R11723-PEA_1_node_25, R11723_PEA1_node_26, R11723_PEA_1_node_27, R11723_PEA_1node_28, R11723-PEA_1_node 29, R11723_PEA_1_node_3, R11723_PEA_1-node_30, R1723_PEA_1node_4, R11723_PEA_1_node_5, R11723_PEA-lnode_6, R11723_PEA-_1node_7 or R11723_PEA_1_node_8.

3. An isolated polypeptide comprising a polypeptide having a sequence selected from the group consisting of: RI 1723_PEA_1_P2, Ri 1723_PEA_1_P6, Ri 1723_PEA-lP7, R11723_PEA_1 P13, or Ri 1723_PEA_1_PlO.

4. An isolated chimeric polypeptide encoding for R1 1723_PEA_1_P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR corresponding to amino acids I - 110 of RI 1723_PEA_1_P6, and a second amino acid sequence WO 2005/072050 PCT/IB2005/000433 1279 being at least 90 % homologous to MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHV RPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 1 - 112 of Q8IXMO, which also corresponds to amino acids 111 222 of RI 1723_PEA-lP6, wherein said first and second amino acid sequences are contiguous and in a sequential order.

5. An isolated polypeptide encoding for a head of RI 1723_PEA__P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR of RI 1723_PEA_1_P6.

6. An isolated chimeric polypeptide encoding for Rl 1723_PEAl-P6, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIIMYRKSCASSAACLIASAG corresponding to amino acids 1 - 83 of Q96AC2, which also corresponds to amino acids 1 - 83 of RI 1723_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order.

7. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the WO 2005/072050 PCT/IB2005/000433 1280 sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723_PEA_1_P6.

8. An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMvYRKSCASSAACLIASAG corresponding to amino acids I - 83 of Q8N2G4, which also corresponds to amino acids I - 83 of R11723_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA-1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order.

9. An isolated polypeptide encoding for a tail of R11723_PEA_1_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in Ri 1723_PEA_1-P6.

10. An isolated chimeric polypeptide encoding for R1 1723_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 24 - 106 of BAC85518, which also corresponds to amino acids 1 - 83 of RI 1723_PEA-lP6, and a second amino acid WO 2005/072050 PCT/IB2005/000433 1281 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEAl_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order.

11. An isolated polypeptide encoding for a tail of RI 1723_PEA_1-P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in Ri 1723_PEA_1_P6.

12. An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFlVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1 - 64 of Q96AC2, which also corresponds to amino acids 1 - 64 of Ri 1723_PEALP7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order.

13. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7. WO 2005/072050 PCT/IB2005/000433 1282

14. An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1 - 64 of Q8N2G4, which also corresponds to amino acids 1 - 64 of RI 1723_PEA_1_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEAl-P7, wherein said first and second amino acid sequences are contiguous and in a sequential order.

15. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7.

16. An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P7, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of RI 1723_PEAl-P7, second amino acid sequence being at least 90 % homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMQSAG corresponding to amino acids 22 - 80 of BAC85273, which also corresponds to amino acids 6 64 of RI 1723_PEA-lP7, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEA_1_P7, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. WO 2005/072050 PCT/IB2005/000433 1283

17. An isolated polypeptide encoding for a head of Ri 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG of RI17 2 3 _PEA_1_P7.

18. An isolated polypeptide encoding for a tail of R I1723_PEA_ 1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7.

19. An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 24 - 87 of BAC855 18, which also corresponds to amino acids 1 - 64 of RI 1723_PEA_1_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of R1 1723-PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order.

20. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723-PEA_1_P7.

21. An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P13, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of RI1723_PEAP13, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most WO 2005/072050 PCT/IB2005/000433 1284 preferably at least 95% honologous to 4 polypeptide having the sequence DTKRTNTLLFEMRBFAKQLTT corresponding to amino acids 64 - 84 of Ri 1723_PEA_1_P13, wherein said ficst and second amino acid sequences are contiguous and in a sequential order.

22. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT in Ri 1723_PEA_1_P13.

23. An isolated chimeric polypeptide encoding for RI 1723_PEA_1_PlO, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of RI 1723_PEALP10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_1_P10, wherein said first and second amino acid sequences are contiguous and in a sequential order.

24. An isolated polypeptide encoding for a tail of Ri 1723_PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_P10.

25. An isolated chimeric polypeptide encoding for Rl 1723_PEA_1_P10, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of QSN2G4, which also corresponds to amino acids 1 - 63 of RI 1723_PEA-lPIO, and a second amino acid sequence being at least 70%, WO 2005/072050 PCT/IB2005/000433 1285 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of Ri 1723_PEA_1_P10, wherein said first and second amino acid sequences are contiguous and in a sequential order.

26. An isolated polypeptide encoding for a tail of RI 1723_PEAi_PO, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in Ri 1723_PEAi_PlO.

27. An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_PlO, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of RI 1723_PEAL-P10, second amino acid sequence being at least 90 % homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 22 - 79 of BAC85273, which also corresponds to amino acids 6 63 of RI 1723_PEA_1_PlO, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_1._Pl, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

28. An isolated polypeptide encoding for a head of RI 1723_PEA_1_PlO, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG of Ri 1723-PEA_1_P10. WO 2005/072050 PCT/IB2005/000433 1286

29. An isolated polypeptide encoding for a tail of RI 1723_PEA_1_PO, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PlO.

30. An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_P10, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 24 - 86 of BAC85518, which also corresponds to amino acids I - 63 of RI 1723_PEALP10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_iPO, wherein said first and second amino acid sequences are contiguous and in a sequential order.

31. An isolated polypeptide encoding for a tail of Ri 1723_PEA_1_PlO, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in R1 1723_PEA-1_P10.

32. An isolated oligonucleotide, comprising an amplicon selected from the group consisting of SEQ ID NOs: 891 or 894.

33. A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of claim 32.

34. The primer pair of claim 33, comprising a pair of isolated oligonucleotides selected from the group consisting of: SEQ NOs 889 and 890; or 892 and 893. WO 2005/072050 PCT/IB2005/000433 1287

35. An antibody capable of specifically binding to an epitope of an amino acid sequence of any of claims 3-31.

36. The antibody of claim 35, wherein said amino acid sequence comprises said tail of claims 4-31.

37. The antibody of claims 35 or 36, wherein said antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein PSEC.

38. A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to any of the above claims.

39. The kit of claim 38, wherein said kit comprises a NAT-based technology.

40. The kit of claim 39, wherein said kit further comprises at least one primer pair capable of selectively hybridizing to a nuc leic acid sequence according to claims 1 or 2.

41. The kit of claim 38, wherein said kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence according to claims 1 or 2.

42. The kit of claim 38, wherein said kit comprises an antibody according to any of claims 35-37.

43. The kit of claim 42, wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot.

44. A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to any of the above claims. WO 2005/072050 PCT/IB2005/000433 1288

45. The method of claim 44, wherein said detecting overexpression is performed with a NAT-based technology.

46. The method of claim 44, wherein said detecting overexpression is performed with an immunoassay.

47. The method of claim 46, wherein said immunoassay comprises an antibody according to any of the above claims.

48. A biomarker capable of detecting breast cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof.

49. A method for screening for breast cancer, comprising detecting breastcancer cells with a biomarker or an antibody or a method or assay according to any of the above claims.

50. A method for diagnosing breast cancer, comprising detecting breast cancer cells with a biomarker or an antibody or a method or assay according to any of the above claims.

51. A method for monitoring disease progression and/or treatment efficacy and/or relapse of breast cancer, comprising detecting breast cancer cells with a biomarker or an antibody or a method or assay according to any of the above claims.

52. A method of selecting a therapy for breast cancer, comprising detecting breast cancer cells with a biomarker or an antibody or a method or assay according to any of the above claims and selecting a therapy according to said detection.