Germline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy.

ABSTRACT: With age, clonal expansions occur pervasively across normal tissues yet only in rare instances lead to cancer, despite being driven by well-established cancer drivers. Characterization of the factors that influence clonal progression is needed to inform interventional approaches. Germline genetic variation influences cancer risk and shapes tumor mutational profile, but its influence on the mutational landscape of normal tissues is not well known. Here we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 new CH-predisposition genes, most of which predispose to CH driven by specific mutational events. CH-predisposition genes contribute to unique somatic landscapes, reflecting the influence of germline genetic backdrop on ge

SUBMITTER: Liu J 

PROVIDER: S-EPMC12339400 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature