The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high-grade serous ovarian cancer: a national retrospective audit

Frugtniet, B., Morgan, S., Murray, A., Palmer-Smith, S., White, R., Jones, Rhys, Hanna, L., Fuller, C., Hudson, E., Mullard, A. and Quinton, A.E. 2022. The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high-grade serous ovarian cancer: a national retrospective audit. BJOG: An International Journal of Obstetrics and Gynaecology 129 (3) , pp. 433-422. 10.1111/1471-0528.16975

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License
Publisher:	Wiley
ISSN:	1470-0328
Date of First Compliant Deposit:	19 November 2021
Date of Acceptance:	12 September 2021
Last Modified:	23 May 2023 22:51
URI:	https://orca.cardiff.ac.uk/id/eprint/145626

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