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Real-world concordance between germline and tumour BRCA1/2 status in epithelial ovarian cancer
Morgan, Robert D Burghel, G. J. Schlecht, H. Clamp, A. R. Hasan, J. Mitchell, C. L. Salih, Z. Shaw, J. Desai, S. Jayson, G. C.
Morgan, Robert D
Burghel, G. J.
Schlecht, H.
Clamp, A. R.
Hasan, J.
Mitchell, C. L.
Salih, Z.
Shaw, J.
Desai, S.
Jayson, G. C.
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Abstract
Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice((R)) companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice((R)) CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice((R)) CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged < 79 years old, with germline BRCA1/2 testing only necessary for patients aged >/= 80 years old with a tumour BRCA1/2 pathogenic variant.
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Date
2023
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Article
Citation
Morgan RD, Burghel GJ, Schlecht H, Clamp AR, Hasan J, Mitchell CL, et al. Real-World Concordance between Germline and Tumour BRCA1/2 Status in Epithelial Ovarian Cancer. Cancers (Basel). 2023 Dec 29;16(1). PubMed PMID: 38201604. Pubmed Central PMCID: 10778166.