Tumor and germline testing with next generation sequencing in epithelial ovarian cancer: a prospective paired comparison using an 18‐gene panel

Genetic testing in epithelial ovarian cancer (EOC) in Ontario includes germline next‐generation sequencing (NGS) for 19 genes. Additionally, tumor tissue undergoes reflex NGS testing for BRCA1/2 to assess eligibility for PARPi. Although parallel testing confers advantages, this model duplicates healthcare resources. Here, we prospectively assessed the feasibility of tumor‐first multigene testing by comparing tumor tissue with germline testing of peripheral blood. An 18‐gene NGS panel was used to test tumor and germline DNA ( n  = 106 patients). In 26 patients, 27 tumor Tier I or II variants were identified, with 16/27 (59%) being germline pathogenic variants (PV) (13 BRCA1/2 ; 3 other genes) and 11/27 (41%) somatic variants (9 BRCA1/2 ; 2 other). In 51/106 patients, there were no tumor variants (excluding TP53 ), of which one patient had a germline BRCA1 copy number variant deletion in exon 12. Tumor‐first testing detected variant‐positive and variant‐negative germline cases in 105/106 patients (99.1%). Among 50 BRCA ‐negative patients, 14/50 (28%) were homologous recombination deficiency (HRD)‐positive. Therefore, we demonstrate that multigene NGS tumor‐testing is effective in identifying germline variants in EOC with a < 1% false‐negative rate.