Mechanisms of APOBEC3 mutagenesis in human cancer cells.

ABSTRACT: The APOBEC3 family of cytosine deaminases has been implicated in some of the most prevalent mutational signatures in cancer^1-3. However, a causal link between endogenous APOBEC3 enzymes and mutational signatures in human cancer genomes has not been established, leaving the mechanisms of APOBEC3 mutagenesis poorly understood. Here, to investigate the mechanisms of APOBEC3 mutagenesis, we deleted implicated genes from human cancer cell lines that naturally generate APOBEC3-associated mutational signatures over time⁴. Analysis of non-clustered and clustered signatures across whole-genome sequences from 251 breast, bladder and lymphoma cancer cell line clones revealed that APOBEC3A deletion diminished APOBEC3-associated mutational signatures. Deletion of both APOBEC3A and

SUBMITTER: Petljak M 

PROVIDER: S-EPMC9329121 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature