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

Robert D. Morgan, George J. Burghel, Nicola Flaum , Michael Bulman, Philip Smith, Andrew R. Clamp, Jurjees Hasan, Claire L. Mitchell, Zena Salih, Emma R. Woodward, Fiona Lalloo, Emma J. Crosbie, Richard J. Edmondson, Andrew J. Wallace, Gordon C. Jayson, D. Gareth R. Evans

Research output: Contribution to journalArticlepeer-review


National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for both germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive NMEOC cases (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 full germline BRCA1/2 database, there were gBRCA PV detected in 92/1114 (8.3%) non-familial (only 3% ≥70 years old) and 245/641 (38.2%) in familial NMEOC cases. Germline non-familial cases were dominated by BRCA2 in older women (8/271 ≥70 years old, all BRCA2; P=0.005). 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 only testing 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 no family history of breast, ovarian, prostate and/or pancreatic cancer.
Original languageEnglish
Publication statusAccepted/In press - 22 Feb 2022

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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