Copy number deletion of RAD50 as predictive marker of BRCAness and PARP inhibitor response in BRCA wild type ovarian cancer.

ABSTRACT:

Objective

To identify novel prognostic and therapeutic markers for PARP inhibitors in BRCA wild type ovarian cancer (OvCa).

Methods

BRCAness status was defined by analyzing whole-exome deep sequencing data from 220 BRCAwt OvCa cases in TCGA. Thirty-three DNA-repair genes were screened in an integrated manner for BRCA-independent mechanism of BRCAness using multiple-dimensional genomic data. Publicly available databases and siRNA knock-down were used for external validation and evaluation of drug response in OvCa cell lines.

Results

In 220 BRCAwt OvCa patients, tumors exhibiting the BRCAness signature have enhanced OS (HR [95% CI]=0.33 [0.15-0.69], P=0.004) and PFS (HR [95% CI]=0.51 [0.24-1.08], P=0.077), strongly suggesting a BRCA-independent mechanism of drug sensiti

SUBMITTER: Zhang M 

PROVIDER: S-EPMC4967351 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature