Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer
dc.contributor.author | Morgan, Robert David | |
dc.contributor.author | Burghel, G. J. | |
dc.contributor.author | Flaum, Nicola | |
dc.contributor.author | Bulman, M. | |
dc.contributor.author | Smith, P. | |
dc.contributor.author | Clamp, Andrew R | |
dc.contributor.author | Hasan, Jurjees | |
dc.contributor.author | Mitchell, Claire L | |
dc.contributor.author | Salih, Zena|Woodward, E. R. | |
dc.contributor.author | Lalloo, F. | |
dc.contributor.author | Shaw, J. | |
dc.contributor.author | Desai, Sudha | |
dc.contributor.author | Crosbie, E. J. | |
dc.contributor.author | Edmondson, R. J. | |
dc.contributor.author | Schlecht, H. | |
dc.contributor.author | Wallace, A. J. | |
dc.contributor.author | Jayson, Gordon C | |
dc.contributor.author | Evans, D. G. R. | |
dc.date.accessioned | 2022-08-01T09:07:07Z | |
dc.date.available | 2022-08-01T09:07:07Z | |
dc.date.issued | 2022 | en |
dc.identifier.citation | Morgan RD, Burghel GJ, Flaum N, Bulman M, Smith P, Clamp AR, et al. Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer. Journal of Clinical Pathology. BMJ; 2022. | en |
dc.identifier.pmid | 35738887 | en |
dc.identifier.doi | 10.1136/jcp-2022-208369 | en |
dc.identifier.uri | http://hdl.handle.net/10541/625390 | |
dc.description.abstract | Aims: Clinical guidelines recommend testing both germline and tumour DNA for BRCA1/2 pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour BRCA1/2 PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline BRCA1/2 PVs. Methods: An observational study that included all tumour BRCA1/2 PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumour BRCA1/2 PVs were compared with PVs recorded in a prospectively gathered pan-cancer germline BRCA1/2 (gBRCA) testing database for the same geographical region (gBRCA1 PVs=910 and gBRCA2 PVs=922). Tumour BRCA1/2 PVs were categorised as common (≥1%), uncommon (<1%) or absent from the germline database. Results: One hundred and thirteen tumour BRCA1/2 PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCA and somatic BRCA1/2 (sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test p<0.0001). All sBRCA PVs were detected in non-familial cases. All tumour BRCA1/2 PVs with a variant allele frequency (VAF) <35% in non-familial cases were somatic variants. Eighty-one per cent of germline-tumour BRCA1/2 PVs were present (common=31, uncommon=25) in the gBRCA testing database, while 89% of somatic-tumour BRCA1/2 PVs were absent (n=39). Conclusions: We predict the likelihood of a tumour BRCA1/2 PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality. | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1136/jcp-2022-208369 | en |
dc.title | Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer | en |
dc.type | Article | en |
dc.contributor.department | Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK | en |
dc.identifier.journal | Journal of Clinical Pathology | en |
dc.description.note | en] | |
refterms.dateFOA | 2022-08-01T12:49:59Z |