Integration of Germline and Somatic Variation Improves Chronic Lymphocytic Leukemia Risk Stratification.

ABSTRACT: Both acquired mutations and germline genetic variation are known risk factors for chronic lymphocytic leukemia (CLL). The joint characterization of germline, acquired, and clinical risk has the potential to improve CLL risk prediction. In this study, we investigated whether the inclusion of a CLL-associated polygenic score (PGS) and two common types of clonal hematopoiesis (CH), autosomal mosaic chromosomal alterations (mCA) and CH of indeterminate potential (CHIP), could improve CLL risk stratification in 436,784 participants in the UK Biobank and a replication set of 35,382 participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Individual mCAs on chromosomes 11, 12, 23, 14, and 22, as well as CHIP mutations in known lymphoid driver genes, were strongly associa

SUBMITTER: Hubbard AK 

PROVIDER: S-EPMC12263322 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature