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dc.contributor.authorMorgan, Robert David
dc.contributor.authorBurghel, G. J.
dc.contributor.authorFlaum, Nicola
dc.contributor.authorBulman, M.
dc.contributor.authorSmith, P.
dc.contributor.authorClamp, Andrew R
dc.contributor.authorHasan, Jurjees
dc.contributor.authorMitchell, Claire L
dc.contributor.authorSalih, Zena|Woodward, E. R.
dc.contributor.authorLalloo, F.
dc.contributor.authorShaw, J.
dc.contributor.authorDesai, Sudha
dc.contributor.authorCrosbie, E. J.
dc.contributor.authorEdmondson, R. J.
dc.contributor.authorSchlecht, H.
dc.contributor.authorWallace, A. J.
dc.contributor.authorJayson, Gordon C
dc.contributor.authorEvans, D. G. R.
dc.date.accessioned2022-08-01T09:07:07Z
dc.date.available2022-08-01T09:07:07Z
dc.date.issued2022en
dc.identifier.citationMorgan 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.pmid35738887en
dc.identifier.doi10.1136/jcp-2022-208369en
dc.identifier.urihttp://hdl.handle.net/10541/625390
dc.description.abstractAims: 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.isoenen
dc.relation.urlhttps://dx.doi.org/10.1136/jcp-2022-208369en
dc.titlePredicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian canceren
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UKen
dc.identifier.journalJournal of Clinical Pathologyen
dc.description.noteen]
refterms.dateFOA2022-08-01T12:49:59Z


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