Multigene germline and somatic testing for epithelial ovarian cancer in China

Background Targeted sequencing has proven invaluable in evaluating BRCA1/2 and homologous recombination repair (HR) pathway genes in epithelial ovarian cancer (EOC). Comprehensive analysis of germline and somatic HR-related gene variants is critical to understanding their clinical significance. This study aims to explore the significance of such variants in Chinese EOC patients. Materials and Methods We analyzed 229 EOC patients using a 21-gene ovarian cancer panel and 141 patients with a 508-gene pan-cancer panel. Germline and somatic variants in the 21 HR-related genes were identified and interpreted. Variant frequencies were calculated, and overall survival (OS) and progression-free survival (PFS) were compared between carriers and non-carriers of BRCA1, BRCA2, and HR-related gene mutations. Responses to platinum-based chemotherapy and the PARP inhibitor Niraparib were also assessed. Results Among the 229 patients, 17.9% carried BRCA1 mutations, 3.5% carried BRCA2 mutations, and 23.1% had mutations in HR-related genes. TP53 was the most common somatic mutation (66.4%). When both germline and somatic mutations were included, BRCA1 and BRCA2 mutation rates rose to 23.6% and 6.1%, respectively. Survival analyses (n=200) showed significantly longer OS for BRCA1/2 and HR-related mutation carriers (germline+somatic) compared to non-carriers under "LP+" (pathogenic/likely pathogenic variants) and "VUS+" (including variants of uncertain significance). Improved OS was observed for BRCA2 mutation carriers and BRCA1/2 somatic mutation carriers under VUS+ strategies. The hazard ratio for OS was lower in the VUS+ group, indicating enhanced predictive performance. Conclusions BRCA1/2 and HR-related mutations are associated with improved OS and sensitivity to therapy. Integrating germline, somatic, and VUS data enhances survival prediction and treatment guidance, underscoring the need for comprehensive genetic assessments in EOC management.