Tumor and germline next generation sequencing in high grade serous cancer: experience from a large population‐based testing program

Abstract

The aim of this study was to determine the prevalence of somatic and germline pathogenic variants (PVs) in high‐grade serous cancer (HGSC) and to demonstrate the technical feasibility and effectiveness of a large‐scale, population‐based tumor testing program. It involved a retrospective review of genetic test results in 600 consecutive HGSC tumor samples and a subsequent comparison of germline and tumor results in a subset of 200 individuals. Tumor testing was successful in 95% of samples (570/600) with at least one BRCA1/2 PV identified in 16% (93/570) of cases. Among the 200 paired cases, BRCA1/2 PVs were detected in 38 tumors (19%); 58% were somatic (22/38); and 42% were germline (16/38). There was 100% concordance between germline and tumor test results. This is the largest series of BRCA1/2 testing in HGSC (tumor‐only and paired cohorts), reported to date, and our data show that an effectively designed and validated population‐based tumor testing program can be used to determine both treatment eligibility and hereditary cancer risk.

Keywords

• BRCA1/BRCA2
• germline variant
• high‐grade serous cancer
• next‐generation sequencing
• somatic variant
• tumor testing