Germline genome analysis of 4,000 cancers from Mutographs project

Abstract

In our proposal, we aim to explore Mutographs data to investigate the interplay between germline and somatic genomes from 4,000 patients spanning across 5 continents and encompassing 7 different types of cancer. Our primary objective is to comprehensively examine the role played by germline pathogenic variants (GPVs) in the development of cancer. Firstly, we will investigate the landscape of GPVs across different cancer types and populations. Moreover, we will assess the effects of germline variants on preferential co-occurrence with oncogenic drivers, somatic mutations patterns and hallmarks of environmental exposures by comparing hereditary and sporadic cancers. We expect that by studying this globally diverse cohort, we will reveal important inherited mechanisms of tumorigenesis operating from the earliest steps disease progression. Additionally, investigating hereditary cancer predisposition syndromes can provide valuable insights into understanding the abnormal biology of cancer. These insights may reveal new strategies for preventing and treating both hereditary and sporadic cases of cancer, thus facilitating the translation of genetic knowledge into improved clinical care.