| Literature DB >> 35260807 |
Robert D Morgan1,2, George J Burghel3, Nicola Flaum4,5, Michael Bulman3, Philip Smith3, Andrew R Clamp4,6, Jurjees Hasan4, Claire L Mitchell4, Zena Salih4, Emma R Woodward5,7, Fiona Lalloo7, Emma J Crosbie6,8, Richard J Edmondson6,8, Andrew J Wallace3, Gordon C Jayson4,6, D Gareth R Evans5,7.
Abstract
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.Entities:
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Year: 2022 PMID： 35260807 PMCID： PMC9276796 DOI： 10.1038/s41416-022-01773-y
Source DB: PubMed Journal: Br J Cancer ISSN： 0007-0920 Impact factor: 9.075