Clinical Impact of Somatic Variants in Homologous Recombination Repair-Related Genes in Ovarian High-Grade Serous Carcinoma

Abstract

PurposeIn this study, we investigated the frequencies of mutations in DNA damage repair genes including <i>BRCA1</i>, <i>BRCA2</i>, homologous recombination genes and <i>TP53</i> gene in ovarian high-grade serous carcinoma, alongside those of germline and somatic <i>BRCA</i> mutations, with the aim of improving the identification of patients suitable for treatment with poly(ADP-ribose) polymerase inhibitors.Materials and MethodsTissue samples from 77 Korean patients with ovarian high-grade serous carcinoma were subjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repair genes and <i>TP53</i> gene and their relationships with patient survival were examined. Additionally, we analyzed <i>BRCA</i> germline variants in blood samples from 47 of the patients for comparison.Results<i>BRCA1</i>, <i>BRCA2</i>, and <i>TP53</i> mutations were detected in 28.6%, 5.2%, and 80.5% of the 77 patients, respectively. Alterations in <i>RAD50, ATR, MSH6, MSH2</i>, and <i>FANCA</i> were also identified. At least one mutation in a DNA damage repair gene was detected in 40.3% of patients (31/77). Germline and somatic <i>BRCA</i> mutations were found in 20 of 47 patients (42.6%), and four patients had only somatic mutations without germline mutations (8.5%, 4/47). Patients with DNA damage repair gene alterations with or without <i>TP53</i>mutation, exhibited better disease-free survival than those with <i>TP53</i> mutation alone.ConclusionDNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma, with somatic <i>BRCA</i> mutations in the absence of germline mutation in 8.5%. Somatic variant examination, along with germline testing of DNA damage repair genes, has potential to detect additional candidates for PARP inhibitor treatment.