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

## TL;DR

This study shows that testing tumor tissue first with an 18-gene panel can effectively identify genetic variants in ovarian cancer patients, reducing the need for duplicate germline testing.

## Contribution

The study demonstrates the feasibility and accuracy of tumor-first multigene testing for germline variant detection in epithelial ovarian cancer.

## Key findings

- Tumor-first testing detected germline pathogenic variants in 59% of identified tumor variants.
- Only 1% of patients had a false-negative result for germline variants using tumor-first testing.
- 28% of BRCA-negative patients were homologous recombination deficiency (HRD)-positive.

## Abstract

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.

Genetic testing in epithelial ovarian cancer includes both germline and tumor‐testing. This approach often duplicates resources. The current prospective study assessed the feasibility of tumor‐first multigene testing by comparing tumor tissue with germline testing of peripheral blood using an 18‐gene NGS panel in 106 patients. This method for identifying germline variants is feasible and effective with a < 1% false‐negative rate.