Identification of novel exonic variants responsible for hereditary breast and ovarian cancer in West Indian population

Abstract

Background Breast and ovarian cancers are the most common cancer types in females in India which pertain to higher mortality and morbidity due to late diagnosis and poor prognosis. Early diagnosis for better prognosis improve the patient’s treatment and survival. The next-generation sequencing (NGS)-based screening has accelerated molecular diagnosis of various cancers. Methods We performed whole exome sequencing (WES) of 30 patients who had a first or second degree relative with breast or ovarian cancer. Further, all these patients are tested negative for BRCA1/2 or other high and moderate risk genes reported for HBOC. WES data from 30 patients were analyzed and variants were called using bcftools. Functional annotation of variants and variant prioritization was performed by Exomiser. The clinical significance of variants was determined by Varsome tool. The functional analysis of genes was determined by STRING analysis and disease association was determined by open target tool. Results We examined the variants based on the prevalence of variants among 30 patients i.e. frequency and disease association determined by the phenotype score of exomiser. From both the approaches, we found novel variants and novel gene candidates associated with HBOC conditions. The variants in HYDIN, AVIL, IWS1, PLA2G6, PRDM4, ST3GAL2, and ZNF717 were predicted highly oncogenic. Moreover, we also found 59 genes having higher phenotype score (phenotype score >0.75) and which are associated with various biological processes such as DNA integrity maintenance, transcriptional regulation, cell cycle and apoptosis. Conclusion The gene variants associated with HBOC condition in West Indian cohort have been revisited. Our findings provide novel as well as highly prevalent variants in the population which could be further studied in detail for their use in early diagnosis and better prognosis of HBOC patients.