Tumor and germline testing with next generation sequencing in epithelial ovarian cancer: a prospective paired...

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.