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Molecular Diagnostics

BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?


National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (n = 388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.7%) were detected in 350 cases with germline BRCA1/2 (gBRCA) wild-type. All sBRCA PVs were detected in non-familial cases. By analysing our regional germline BRCA1/2 database there were 92/1114 (8.3%) gBRCA PVs detected in non-familial cases (only 3% ≥70 years old) and 245/641 (38.2%) in familial cases. Germline non-familial cases were dominated by BRCA2 in older women (8/271 ≥ 70 years old, all BRCA2). The ratio of sBRCA-to-gBRCA was ≤1.0 in women aged <70 years old, compared to 5.2 in women aged ≥70 years old (P = 0.005). The likelihood of missed germline BRCA1/2 PVs (copy-number variants missed on most somatic assays) by testing only tumour DNA was 0.4% in women aged ≥70 years old. We recommend reflex tumour BRCA1/2 testing in all NMEOC cases, and that gBRCA testing is not required for women aged ≥70 years old with no identifiable tumour BRCA1/2 PV and/or family history of breast, ovarian, prostate and/or pancreatic cancer.

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Fig. 1: Flow chart for germline and tumour BRCA1/2 testing.


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ERW and DGRE are supported by the Manchester National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (IS-BRC-1215-20007). EJC is supported by a NIHR Advanced Fellowship (NIHR300650). NF is supported by CRUK via the funding to Cancer Research UK Manchester Centre: [C147/A18083] and [C147/A25254].


The tumour BRCA1/2 testing service was funded by AstraZeneca and Merck Sharp & Dohme, who gave permission to publish the data. Neither company had any influence in the writing of the manuscript or the views expressed by the authors.

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Authors and Affiliations



RDM and DGRE designed and initiated the study. RDM, NF, ARC, JH, CLM, ZS, ERW, FL, EJC, RJE, GCJ and DGRE gained consent for germline and tumour BRCA1/2 testing. GJB, MB, PS and AJW reported all germline and tumour BRCA1/2 results. All authors interpreted the data and reviewed the final version of the manuscript.

Corresponding author

Correspondence to Robert D. Morgan.

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Competing interests

RDM, GJB, NF, MB, PS, JH, CLM, ZS, ERW, FL, EJC, RJE, AJW and DGRE declare no competing interests. GCJ declares research funding from AstraZeneca for investigator-led clinical trials. ARC declares research funding and advisory boards fees from AstraZeneca, and speaker and advisory board fees from Clovis Oncology.

Ethics approval and consent to participate

All women included in this study provided informed consent to undergo germline and tumour BRCA1/2 testing. The germline BRCA1/2 database is approved by North Manchester Research Ethics Committee (08/H1006/77). The Genetic Variants in Gynaecological Cancer database is approved by the Christie NHS Foundation Trust (59).

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Morgan, R.D., Burghel, G.J., Flaum, N. et al. BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?. Br J Cancer (2022).

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