Real-World Concordance between Germline and Tumour Status in Epithelial Ovarian Cancer.

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour / testing followed by germline testing in patients with a positive tumour test result. This testing model relies on tumour / tests being able to detect all types of pathogenic variant. We analysed germline and tumour test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour testing was performed using the next-generation sequencing (NGS)-based myChoice companion diagnostic (CDx; Myriad Genetics, Inc.). Germline 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 and variants. Of these, 367 (96.1%) patients were tested for germline / variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a / pathogenic variant (36 germline and 20 somatic). All germline pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline 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 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice CDx is used for tumour testing, our data supports a testing strategy of germline and tumour testing in all patients diagnosed with epithelial ovarian cancer aged < 79 years old, with germline testing only necessary for patients aged ≥ 80 years old with a tumour pathogenic variant.