Sequence dependencies and mutation rates of localized mutational processes in cancer.

Background: Cancer mutations accumulate through replication errors and DNA damage coupled with incomplete repair. Individual mutational processes often show nucleotide sequence and functional region preferences. As a result, some sequence contexts mutate at much higher rates than others, with additional variation found between functional regions.

Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns.

DNA repair deficiencies in cancers may result in characteristic mutational patterns, as exemplified by deficiency of and efficacy prediction for PARP inhibitors. We trained and evaluated predictive models for loss-of-function (LOF) of 145 individual DNA damage response genes based on genome-wide mutational patterns, including structural variants, indels, and base-substitution signatures. We identified 24 genes whose deficiency could be predicted with good accuracy, including expected mutational patterns for , , , and LOF variants.