Identification of a signature of evolutionarily conserved stress-induced mutagenesis in cancer.

ABSTRACT: The clustering of mutations observed in cancer cells is reminiscent of the stress-induced mutagenesis (SIM) response in bacteria. Bacteria deploy SIM when faced with DNA double-strand breaks in the presence of conditions that elicit an SOS response. SIM employs DinB, the evolutionary precursor to human trans-lesion synthesis (TLS) error-prone polymerases, and results in mutations concentrated around DNA double-strand breaks with an abundance that decays with distance. We performed a quantitative study on single nucleotide variant calls for whole-genome sequencing data from 1950 tumors, non-inherited mutations from 129 normal samples, and acquired mutations in 3 cell line models of stress-induced adaptive mutation. We introduce statistical methods to identify mutational clusters, qua

SUBMITTER: Cisneros LH 

PROVIDER: S-EPMC9488704 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature