Patients diagnosed with epithelial ovarian cancer may undergo reflex tumourBRCA1/2testing followed by germlineBRCA1/2testing in patients with a positive tumour test result. This testing model relies on tumourBRCA1/2tests being able to detect all types of pathogenic variant. We analysed germline and tumourBRCA1/2test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. TumourBRCA1/2testing was performed using the next-generation sequencing (NGS)-based myChoice®companion diagnostic (CDx; Myriad Genetics, Inc.). GermlineBRCA1/2testing 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 tumourBRCA1andBRCA2variants. Of these, 367 (96.1%) patients were tested for germlineBRCA1/2variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had aBRCA1/2pathogenic variant (36 germline and 20 somatic). All germlineBRCA1/2pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germlineBRCA1/2pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germlineBRCA1/2pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice®CDx was able to detect most germlineBRCA1/2pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad’s myChoice®CDx is used for tumourBRCA1/2testing, our data supports a testing strategy of germline and tumourBRCA1/2testing in all patients diagnosed with epithelial ovarian cancer aged < 79 years old, with germlineBRCA1/2testing only necessary for patients aged ≥ 80 years old with a tumourBRCA1/2pathogenic variant.
被诊断为上皮性卵巢癌的患者可能接受肿瘤BRCA1/2检测，若肿瘤检测结果呈阳性，则进一步进行胚系BRCA1/2检测。该检测模式依赖于肿瘤BRCA1/2检测能够识别所有类型的致病性变异。我们分析了在我们专科肿瘤转诊中心接受治疗的上皮性卵巢癌患者的胚系和肿瘤BRCA1/2检测结果。肿瘤BRCA1/2检测采用基于新一代测序（NGS）的myChoice®伴随诊断（CDx；Myriad Genetics, Inc.）。胚系BRCA1/2检测在西北基因组学实验室中心进行，采用NGS和多重连接依赖性探针扩增技术。2021年4月11日至2023年10月11日期间，共有382名患者成功接受了肿瘤BRCA1和BRCA2变异检测。其中，367名（96.1%）患者接受了胚系BRCA1/2变异检测。在接受肿瘤和胚系检测的患者中，15.3%（56/367）携带BRCA1/2致病性变异（36例为胚系，20例为体细胞）。所有胚系BRCA1/2致病性小片段测序变异均在肿瘤DNA中检出。相比之下，8例胚系BRCA1/2致病性大片段重排中有3例未在肿瘤DNA检测报告中显示。胚系DNA与肿瘤DNA中检出的胚系BRCA1/2致病性变异总体一致性为91.7%（33/36），在临床上可接受。myChoice® CDx能够检测出肿瘤DNA中的大多数胚系BRCA1/2致病性变异，尽管一部分致病性大片段重排未被报告。如果使用Myriad的myChoice® CDx进行肿瘤BRCA1/2检测，我们的数据支持对年龄<79岁的所有确诊上皮性卵巢癌患者进行胚系和肿瘤BRCA1/2检测的策略，而对于年龄≥80岁且肿瘤BRCA1/2检测呈致病性变异的患者，仅需进行胚系BRCA1/2检测。
Real-World Concordance between Germline and TumourBRCA1/2Status in Epithelial Ovarian Cancer
肿瘤(癌症)患者之家