Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies.

ABSTRACT: The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers sensitivity to PARP inhibitors and platinum-therapies. Somatic reversion mutations restoring BRCA1/2 function mediate resistance, and have exclusively been reported in BRCA-associated tumors. In this study, we analyze matched tumor and normal sequencing from 31,927 patients and identify 846 (2.7%) patients with germline BRCA1/2 variants across 43 different cancer types, including 11 with somatic reversion mutations. While nine are in BRCA-associated tumors, we find two reversion mutations in non-BRCA-associated histologies, namely lung and esophagogastric adenocarcinomas. Both were

SUBMITTER: Murciano-Goroff YR 

PROVIDER: S-EPMC9684575 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature