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

Autor: Morgan RD; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester M13 9PL, UK., Burghel GJ; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.; Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK., Schlecht H; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK., Clamp AR; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester M13 9PL, UK., Hasan J; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK., Mitchell CL; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK., Salih Z; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK., Shaw J; Department of Gynaecological Pathology, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK., Desai S; Department of Pathology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK., Jayson GC; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester M13 9PL, UK., Woodward ER; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.; Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.; Department of Clinical Genetics, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK., Evans DGR; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.; Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK.; Department of Clinical Genetics, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Dec 29; Vol. 16 (1). Date of Electronic Publication: 2023 Dec 29.
DOI: 10.3390/cancers16010177
Abstrakt: 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 < 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant.
Databáze: MEDLINE
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