CG>TG mutation frequency as negative predictor of homologous recombination deficiency in ovarian and breast cancer.

ABSTRACT: Homologous recombination deficiency (HRD) is a predictive biomarker for PARP inhibition and platinum-based chemotherapy. While copy number alteration-based scores such as HRDsum = LST + TAI + LOH are included in therapy approvals, single base substitutions (SBS) are underinvestigated as predictors of HRD. WES data of the TCGA pan-cancer cohort and an in-house ovarian cancer cohort were annotated by alterations in BRCA1/2 and additional genes causative of HRD. Using this reference, the new biomarker f_deam defined as frequency of C > T transitions at CpG sites in relation to all SBS and HRDsum were compared for the detection of HRD. In the TCGA ovarian cancer, the in-house, and the TCGA breast cancer cohorts, f_deam performed non-inferior to HRDsum (AUC = 0.84, AUC = 0.8

SUBMITTER: Romanovsky E 

PROVIDER: S-EPMC12307739 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature