Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study
| Autor: | Laura Casey, Lucy Jenkins, Tina Mills-Baldock, Elly Brockbank, D. Gareth Evans, Monika Sobocan, Helene Schlecht, Naomi L. Bowers, Giorgia Trevisan, Faiza Gaba, A Lawrence, Andrew J Wallace, Philip Smith, Rosa Legood, Rekha Wuntakal, Oleg Blyuss, D Chandrasekaran, Mary Quigley, Fatima El Khouly, Shanthini M Crusz, Rowan E. Miller, George J Burghel, Ajith Kumar, Naveena Singh, Munaza Ahmed, Michelle Lockley, Asma Faruqi, Arjun Jeyarajah, Li Sun, M Bulman, Olivia Evans, Rory F L Hammond, Saurabh Phadnis, Ranjit Manchanda |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty endocrine system diseases Somatic cell BRCA BRIP1 germline Article Germline genetic testing Internal medicine medicine Family history Stage (cooking) skin and connective tissue diseases RC254-282 Genetic testing RAD51C somatic medicine.diagnostic_test RAD51D business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer medicine.disease ovarian cancer Ovarian cancer business |
| Zdroj: | Cancers Volume 13 Issue 17 Chandrasekaran, D, Sobocan, M, Blyuss, O, Miller, R E, Evans, O, Crusz, S M, Mills-baldock, T, Sun, L, Hammond, R F L, Gaba, F, Jenkins, L A, Ahmed, M, Kumar, A, Jeyarajah, A, Lawrence, A C, Brockbank, E, Phadnis, S, Quigley, M, El Khouly, F, Wuntakal, R, Faruqi, A, Trevisan, G, Casey, L, Burghel, G J, Schlecht, H, Bulman, M, Smith, P, Bowers, N L, Legood, R, Lockley, M, Wallace, A, Singh, N, Evans, D G & Manchanda, R 2021, ' Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study ', Cancers, vol. 13, no. 17, 4344 . https://doi.org/10.3390/cancers13174344 Cancers, Vol 13, Iss 4344, p 4344 (2021) |
| ISSN: | 2072-6694 |
| Popis: | We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed > 1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes. |
| Databáze: | OpenAIRE |
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