Loading...
Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer
Morgan, Robert David Burghel, G. J. Flaum, Nicola Bulman, M. Smith, P. Clamp, Andrew R Hasan, Jurjees Mitchell, Claire L Salih, Zena|Woodward, E. R. Lalloo, F.
Morgan, Robert David
Burghel, G. J.
Flaum, Nicola
Bulman, M.
Smith, P.
Clamp, Andrew R
Hasan, Jurjees
Mitchell, Claire L
Salih, Zena|Woodward, E. R.
Lalloo, F.
Citations
Altmetric:
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.
Description
Date
2022
Publisher
Collections
Files
Keywords
Type
Article
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.