BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?
AuthorsMorgan, Robert David
Clamp, Andrew R
Mitchell, Claire L
Woodward, E R
Jayson, G. C.
Evans, D G R
AffiliationThe Christie NHS Foundation Trust, Manchester
MetadataShow full item record
AbstractNational 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.
CitationMorgan, R D, Burghel, G J, Flaum, N, Bulman, M, Smith, P, Clamp, A R, Hasan, J, Mitchell, C L, Salih, Z, Woodward, E R, Lalloo, F, Crosbie, E J, Edmondson, R J, Wallace, A J, Jayson, G C, Evans, D G R. BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing? British Journal of Cancer. 2022 Mar 8
JournalBritish Journal of Cancer
- Predicting the likelihood of a <i>BRCA1/2</i> pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.
- Authors: Morgan RD, Burghel GJ, Flaum N, Bulman M, Smith P, Clamp AR, Hasan J, Mitchell C, Salih Z, Woodward ER, Lalloo F, Shaw J, Desai S, Crosbie EJ, Edmondson RJ, Schlecht H, Wallace AJ, Jayson GC, Evans DGR
- Issue date: 2022 Jun 23
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- Authors: Flaum N, Morgan RD, Burghel GJ, Bulman M, Clamp AR, Hasan J, Mitchell CL, Badea D, Moon S, Hogg M, Hadjiyiannakis D, Clancy T, Schlecht H, Woodward ER, Crosbie EJ, Edmondson RJ, Wallace AJ, Jayson GC, Lalloo FI, Harkness EF, Evans DGR
- Issue date: 2020 Nov
- Probability of detecting germline BRCA1/2 pathogenic variants in histological subtypes of ovarian carcinoma. A meta-analysis.
- Authors: Witjes VM, van Bommel MHD, Ligtenberg MJL, Vos JR, Mourits MJE, Ausems MGEM, de Hullu JA, Bosse T, Hoogerbrugge N
- Issue date: 2022 Jan
- Prevalence of germline pathogenic <i>BRCA1/2</i> variants in sequential epithelial ovarian cancer cases.
- Authors: Morgan RD, Burghel GJ, Flaum N, Bulman M, Clamp AR, Hasan J, Mitchell CL, Schlecht H, Woodward ER, Lallo FI, Crosbie EJ, Edmondson RJ, Wallace AJ, Jayson GC, Evans DGR
- Issue date: 2019 May
- Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history.
- Authors: Engel C, Rhiem K, Hahnen E, Loibl S, Weber KE, Seiler S, Zachariae S, Hauke J, Wappenschmidt B, Waha A, Blümcke B, Kiechle M, Meindl A, Niederacher D, Bartram CR, Speiser D, Schlegelberger B, Arnold N, Wieacker P, Leinert E, Gehrig A, Briest S, Kast K, Riess O, Emons G, Weber BHF, Engel J, Schmutzler RK, German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).
- Issue date: 2018 Mar 7