Mismatch repair deficiency endows tumors with a unique mutation signature and sensitivity to DNA double-strand breaks.

ABSTRACT: DNA replication errors that persist as mismatch mutations make up the molecular fingerprint of mismatch repair (MMR)-deficient tumors and convey them with resistance to standard therapy. Using whole-genome and whole-exome sequencing, we here confirm an MMR-deficient mutation signature that is distinct from other tumor genomes, but surprisingly similar to germ-line DNA, indicating that a substantial fraction of human genetic variation arises through mutations escaping MMR. Moreover, we identify a large set of recurrent indels that may serve to detect microsatellite instability (MSI). Indeed, using endometrial tumors with immunohistochemically proven MMR deficiency, we optimize a novel marker set capable of detecting MSI and show it to have greater specificity and selectivity than standard M

SUBMITTER: Zhao H 

PROVIDER: S-EPMC4141275 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature