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

Molecular Oncology

Marcus Q Bernardini¹  Natalie Stickle²  Marjan Rouzbahman²  Blaise Clarke²  Jeanna McCuaig³  Raymond H Kim⁴  Sylvie Grenier⁵  Tracy L. Stockley⁵  Melanie Care⁵ 

[1] Department of Gynecologic Oncology Princess Margaret Hospital Cancer Centre Toronto Canada;Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada;Department of Molecular Genetics University of Toronto Toronto Canada;Familial Cancer Clinic Princess Margaret Hospital Cancer Centre University Health Network Toronto Canada;Laboratory Medicine Program Division of Clinical Laboratory Genetics University Health Network Toronto Canada;

关键词: BRCA1/BRCA2;    germline variant;    high‐grade serous cancer;    next‐generation sequencing;    somatic variant;    tumor testing;   

DOI  :  10.1002/1878-0261.12817

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown