Understanding the prevalence of germline oncogenic biomarker variants across the Indian population

Genomic biomarkers are essential aspects of personalized medicine. They offer an opportunity for early detection and appropriate intervention, thereby leading to improved patient outcomes and cost-effective treatment. However, different populations have varied genetic landscapes, and thus, may have unique biomarkers. Here we study the prevalence of mutation-specific oncogenic biomarkers in the Indian population and analyse their presence across disease cohorts. We annotate the IndiGen data obtained from whole genome sequencing of 1029 self-declared healthy Indian individuals with biomarker information obtained from the OncoKB knowledgebase, a repository of evidence-based information about somatic biomarkers and structural alterations in patient tumours. We further establish the utility of this study by analysing these biomarkers across GUaRDIAN, a nationwide multi-cohort database, and MUSTARD, a repository of mutation-specific therapies in cancer. In this study, we discovered 34 biomarker variants of therapeutic actionability across 16 genes linked to 23 unique drugs or drug combinations in 23 unique types of cancer. In all, we have found 52 biomarker variants with 172 different biomarker types including therapeutic, resistance, diagnostic, and prognostic. We establish that nearly 7% of the population were found to be carriers of at least one of the four evidence-based biomarkers. Finally, we also establish the prevalence of 42 biomarker variants across 23 genes in both AD and AR modes of inheritance. We have calculated the prevalence of cancer biomarkers of therapeutic, diagnostic and prognostic value in the globally underrepresented Indian population. The known biomarker landscape so established can be used for clinical advantage to improve patient care. Cancers without corresponding biomarker matches can also be further studied to discover biomarkers unique to Indian populations.