Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA.

ABSTRACT: Clustered somatic mutations are common in cancer genomes and previous analyses reveal several types of clustered single-base substitutions, which include doublet- and multi-base substitutions^1-5, diffuse hypermutation termed omikli⁶, and longer strand-coordinated events termed kataegis^3,7-9. Here we provide a comprehensive characterization of clustered substitutions and clustered small insertions and deletions (indels) across 2,583 whole-genome-sequenced cancers from 30 types of cancer¹⁰. Clustered mutations were highly enriched in driver genes and associated with differential gene expression and changes in overall survival. Several distinct mutational processes gave rise to clustered indels, including signatures that were enriched in tobacco smo

SUBMITTER: Bergstrom EN 

PROVIDER: S-EPMC8850194 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature