RT Journal Article SR Electronic T1 Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 684 OP 689 DO 10.1136/jcp-2022-208369 VO 76 IS 10 A1 Morgan, Robert D A1 Burghel, George J A1 Flaum, Nicola A1 Bulman, Michael A1 Smith, Philip A1 Clamp, Andrew R A1 Hasan, Jurjees A1 Mitchell, Claire A1 Salih, Zena A1 Woodward, Emma R A1 Lalloo, Fiona A1 Shaw, Joseph A1 Desai, Sudha A1 Crosbie, Emma J A1 Edmondson, Richard J A1 Schlecht, Helene A1 Wallace, Andrew J A1 Jayson, Gordon C A1 Evans, D Gareth R YR 2023 UL http://jcp.bmj.com/content/76/10/684.abstract AB 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.All data relevant to the study are included in the article or uploaded as online supplemental information.