Pathogenic germline mutation hotspots in east Asian cancer genomes.

Abstract

e13011 Background: To summarise the prevalence of pathogenic germline variants in East Asian cancer genomes and to develop an online resource and reference for genetic analysis of cancer susceptible germline mutation hotspots. Methods: We performed the most extensive investigation of germline mutations in East Asian cancer population based on publicly available data collected from multiple institutions over 1,600 patients with 15 cancer types. The pathogenic cancer susceptibility gene mutations were called by analyzing whole exome sequencing data generated from the normal control samples from the cancer patients deposited on the SRA database. Results: Compared with 9,435 East Asian controls in the gnomAD dataset, we identified pathogenic recurrent germline mutations based on our MaGiC analysis pipeline including quality controlled, filtration and annotation. More than 150 variants were found, and the top 3 hotspot mutations are TP53 in 5 types of cancer, BRCA2 in 3 types of cancer and PIK3CA in 4 types of cancer. The hotspot variants(same cancer predisposition gene set, but different pathogenic mutations) were of population difference in comparison with Caucasian population. Conclusions: Our work is the first comprehensive analysis of East Asian cancer predisposition germline mutations. It provides informative references for cancer genetic consulting and early prevention in more than 20% of world population. The update of our database covering larger populations and more cancer types is needed and still ongoing.