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IGF2 is Deregulated During the Development of Uterine Cervical Carcinoma in Indian Patients

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Abstract

Uterine cervical carcinoma (CACX) is one of the leading causes of deaths in Indian women. Chromosomal alterations including 11p15.5 locus were reported in CACX. Consequently, we strived for the first time to understand the molecular status of the candidate gene Insulin-like growth factor 2, IGF2 (11p15.5) in Indian CACX patients (n = 128). DNA copy number (CN) analysis using CGH-SNP analysis showed no genetic alteration and it was further validated by comparison with publicly available CN datasets. But promoter hypo-methylation during the progression of CACX was observed and also found to be concordant with publicly available DNA methylation datasets. Interestingly, we found diverse expression of IGF2 transcript in both normal cervical epithelium (NCE) and CACX tumors. Similar heterogeneous expression pattern was seen in publicly available expression datasets as well. Finally, protein expression analysis in NCE showed concordance with transcript expression but tumors showed frequent low expression. Log-rank test showed a difference (p-value = 0.057) in overall survival between cases with and without alteration for IGF2 in Indian CACX patients. Collectively, our study proposes that regulation of IGF2 expression in NCE appeared to be multifaceted and deregulation during the development of CACX resulted in the differential expression.

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Acknowledgement

The authors thank the Director, Chittaranjan National Cancer Institute, Kolkata, India. This work was supported by UGC-NET/JRF grant [Sr No. 2121130723] to Mr S. Samadder from University Grants Commission (UGC), UGC-NET Fellowship grant (Sr. No. 2061430780, Ref No.: 22/06/2014(i)EU-V) to Ms M. Basu and grant from Council of Scientific & Industrial Research (CSIR), Government of India [No. 60(0111)/14/EMR-II of dt 03/11/2014] to Dr. C. K. Panda.

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Authors and Affiliations

  1. Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700 026, India

    Anirban Roychowdhury, Sudip Samadder, Mukta Basu & Chinmay Kumar Panda

  2. Department of Zoology, Siliguri College, Darjeeling, India

    Dipanjana Indra Mazumder

  3. Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India

    Pijush Das

  4. Department of Gynecology Oncology, Chittaranjan National Cancer Institute, Kolkata, India

    Ranajit Mondal

  5. Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, India

    Anup Roy

  6. Saroj Gupta Cancer Centre & Research Institute, Kolkata, India

    Susanta Roychoudhury

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  1. Anirban Roychowdhury
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  2. Sudip Samadder
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  3. Dipanjana Indra Mazumder
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  4. Pijush Das
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  5. Mukta Basu
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  7. Anup Roy
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  8. Susanta Roychoudhury
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  9. Chinmay Kumar Panda
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Correspondence to Chinmay Kumar Panda.

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Analysis of specificity of primers used for IGF2 transcript. a Representative melting curve (-dF/dT vs temperature) showing one peak indicative of single amplicon. b Representative agarose gel showing single band of the amplicon (293bp) for the CACX samples, post qRT-PCR analysis. Below is the link to the electronic supplementary material.

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Roychowdhury, A., Samadder, S., Indra Mazumder, D. et al. IGF2 is Deregulated During the Development of Uterine Cervical Carcinoma in Indian Patients. Biochem Genet 57, 638–651 (2019). https://doi.org/10.1007/s10528-019-09917-1

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  • DOI: https://doi.org/10.1007/s10528-019-09917-1

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