BRCA loss of function including BRCA1 DNA-methylation, but not BRCA-unrelated homologous recombination deficiency, is associated with platinum hypersensitivity in high-grade ovarian cancer.

ABSTRACT:

Background

In high-grade ovarian cancer (HGOC), determination of homologous recombination deficiency (HRD) status is commonly used in routine practice to predict response to platinum-based therapy or poly (ADP-ribose) polymerase inhibitors (PARPi). Here we tested the hypothesis that BRCA loss of function (LOF) due to epigenetic or genetic aberrations is a better predictor for the clinical outcome than HRD. One hundred thirty-one HGOC tissues were tested for BRCA DNA-methylation, BRCA mutations, HRD and BRCA1 mRNA expression, followed by a comprehensive survival analysis.

Results

BRCA1-methylation was detected in 11% of the tumors, exclusively in BRCA1-wild-type (wt) HGOCs. BRCA1-methylated tumors (BRCA1-meth) had HRD-scores similar to those of BRCA-mutated (mut) tumors, and

SUBMITTER: Fiegl H 

PROVIDER: S-EPMC11603837 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature