A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms.

Ayam Gupta,Jyotsna Batra,Babita Malik,Maneesh Vijay,Devendra Sharma,Nidhi Shukla,Nirmal Kumar Lohiya,Sonal Gupta,Mamta Nehra,Ashwani Kumar Mishra,Prashanth Suravajhala

doi:10.3389/fgene.2020.00874

Abstract

Prostate cancer (PCa) is the third most common cancer among men in India, and no next-generation sequencing (NGS) studies have been attempted earlier. Recent advances in NGS have heralded the discovery of biomarkers from Caucasian/European and Chinese ancestry, but not much is known about the Indian phenotype/variant of PCa. In a pilot study using the whole exome sequencing of benign/PCa patients, we identified characteristic mutations specific to the Indian sub-population. We observed a large number of mutations in DNA repair genes, viz. helicases, TP53, and BRCA besides the variants of unknown significance with a possibly damaging rare variant (rs730881069/chr19:55154172C/TR136Q) in the TNNI3 gene that has been previously reported as a semi-conservative amino acid substitution. Our pilot study attempts to bring an understanding of PCa prognosis and recurrence for the Indian phenotype.

Highlights

Prostate cancer (PCa) is the second most prevalent cancer worldwide and the third most prevalent cancer in India (Jain et al, 2014)
The data show that almost all regions of India are affected, with the incidences of PCa relatively low in some states like Gujarat (Ahmedabad and Wardha Population Based Cancer Registries (PBCRs)) and Madhya Pradesh (Bhopal PBCR), the lowest being the northeast regions of India (Jain et al, 2014)
The false positives were carefully checked between benign prostate hyperplasia (BPH) and PCa samples even as a number of exome sites, low-coverage sites, and large deletions could not be validated

Summary

Introduction

Prostate cancer (PCa) is the second most prevalent cancer worldwide and the third most prevalent cancer in India (Jain et al, 2014). The data show that almost all regions of India are affected, with the incidences of PCa relatively low in some states like Gujarat (Ahmedabad and Wardha PBCRs) and Madhya Pradesh (Bhopal PBCR), the lowest being the northeast regions of India (Jain et al, 2014). This could be because of lack of PBCRs in addition to PCa not actively reported in states where awareness about it is lacking (Kimura, 2012)

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Conclusion