Beyond <i>BRCA</i> deficiency: Clinical and molecular predictors of survival in patients with <i>BRCA</i>-deficient tubo-ovarian high-grade serous carcinoma.

ABSTRACT: BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤3 years, n=42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long

SUBMITTER: Zwimpfer TA 

PROVIDER: S-EPMC12486008 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature