Cancers (Dec 2023)

Real-World Concordance between Germline and Tumour <i>BRCA1/2</i> Status in Epithelial Ovarian Cancer

  • Robert D. Morgan,
  • George J. Burghel,
  • Helene Schlecht,
  • Andrew R. Clamp,
  • Jurjees Hasan,
  • Claire L. Mitchell,
  • Zena Salih,
  • Joseph Shaw,
  • Sudha Desai,
  • Gordon C. Jayson,
  • Emma R. Woodward,
  • D. Gareth R. Evans

DOI
https://doi.org/10.3390/cancers16010177
Journal volume & issue
Vol. 16, no. 1
p. 177

Abstract

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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® 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® 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® 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 BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant.

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