Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status

Abstract

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

Figure 1. Venn diagram representing data availability for N = 1063 invasive EOC patients.

Figure 2. Overall survival for high grade serous EOC by HRD and type of alteration.

(A). Red: HRD; Black: NAD. (B). Above is a depiction of samples with type of alteration in each gene; below are the Kaplan Meier curves. Red: germline deleterious mutation; Green: somatic deleterious mutation; Blue: somatic methylation; Black: no germline mutation, somatic mutation or methylation.