PT - JOURNAL ARTICLE AU - Morgan, Robert D AU - Burghel, George J AU - Flaum, Nicola AU - Bulman, Michael AU - Smith, Philip AU - Clamp, Andrew R AU - Hasan, Jurjees AU - Mitchell, Claire AU - Salih, Zena AU - Woodward, Emma R AU - Lalloo, Fiona AU - Shaw, Joseph AU - Desai, Sudha AU - Crosbie, Emma J AU - Edmondson, Richard J AU - Schlecht, Helene AU - Wallace, Andrew J AU - Jayson, Gordon C AU - Evans, D Gareth R TI - Predicting the likelihood of a <em>BRCA1/2</em> pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer AID - 10.1136/jcp-2022-208369 DP - 2023 Oct 01 TA - Journal of Clinical Pathology PG - 684--689 VI - 76 IP - 10 4099 - http://jcp.bmj.com/content/76/10/684.short 4100 - http://jcp.bmj.com/content/76/10/684.full SO - J Clin Pathol2023 Oct 01; 76 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 (&lt;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&lt;0.0001). All sBRCA PVs were detected in non-familial cases. All tumour BRCA1/2 PVs with a variant allele frequency (VAF) &lt;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.