Objective: To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing.
Design: National retrospective audit.
Setting: The All Wales Medical Genomics Service (AWMGS).
Population: Patients with high-grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS.
Methods: Analysis of NGS data from germline and/or tumour testing.
Main outcome measures: Frequency of BRCA1 and BRCA2 pathogenic variants.
Results: The overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone.
Conclusions: Parallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high-grade serous ovarian cancer.
Tweetable abstract: Parallel germline and tumour testing maximises BRCA pathogenic variant detection in ovarian cancer.
Keywords: BRCA; germline; mainstreamed; oncology-led; ovarian cancer; pathogenic variant; somatic.
© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.