Cancers (Aug 2021)
Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study
- Dhivya Chandrasekaran,
- Monika Sobocan,
- Oleg Blyuss,
- Rowan E. Miller,
- Olivia Evans,
- Shanthini M. Crusz,
- Tina Mills-Baldock,
- Li Sun,
- Rory F. L. Hammond,
- Faiza Gaba,
- Lucy A. Jenkins,
- Munaza Ahmed,
- Ajith Kumar,
- Arjun Jeyarajah,
- Alexandra C. Lawrence,
- Elly Brockbank,
- Saurabh Phadnis,
- Mary Quigley,
- Fatima El Khouly,
- Rekha Wuntakal,
- Asma Faruqi,
- Giorgia Trevisan,
- Laura Casey,
- George J. Burghel,
- Helene Schlecht,
- Michael Bulman,
- Philip Smith,
- Naomi L. Bowers,
- Rosa Legood,
- Michelle Lockley,
- Andrew Wallace,
- Naveena Singh,
- D. Gareth Evans,
- Ranjit Manchanda
Affiliations
- Dhivya Chandrasekaran
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Monika Sobocan
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Oleg Blyuss
- School of Physics, Engineering and Computer Science, University of Hertfordshire, Hatfield AL10 9AB, UK
- Rowan E. Miller
- Department of Medical Oncology, Barts Health NHS Trust, London EC1A 7BE, UK
- Olivia Evans
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Shanthini M. Crusz
- Department of Medical Oncology, Barts Health NHS Trust, London EC1A 7BE, UK
- Tina Mills-Baldock
- Department of Medical Oncology, Barking, Havering & Redbridge University Hospitals, Essex RM7 0AG, UK
- Li Sun
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Rory F. L. Hammond
- Department of Pathology, Barts Health NHS Trust, London E1 1FR, UK
- Faiza Gaba
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Lucy A. Jenkins
- North East Thames Regional Genetics Service, Great Ormond Street Hospital, London WC1N 3JH, UK
- Munaza Ahmed
- North East Thames Regional Genetics Service, Great Ormond Street Hospital, London WC1N 3JH, UK
- Ajith Kumar
- North East Thames Regional Genetics Service, Great Ormond Street Hospital, London WC1N 3JH, UK
- Arjun Jeyarajah
- Department of Gynaecological Oncology, Barts Health NHS Trust, London EC1 1BB, UK
- Alexandra C. Lawrence
- Department of Gynaecological Oncology, Barts Health NHS Trust, London EC1 1BB, UK
- Elly Brockbank
- Department of Gynaecological Oncology, Barts Health NHS Trust, London EC1 1BB, UK
- Saurabh Phadnis
- Department of Gynaecological Oncology, Barts Health NHS Trust, London EC1 1BB, UK
- Mary Quigley
- Department of Medical Oncology, Barking, Havering & Redbridge University Hospitals, Essex RM7 0AG, UK
- Fatima El Khouly
- Department of Medical Oncology, Barking, Havering & Redbridge University Hospitals, Essex RM7 0AG, UK
- Rekha Wuntakal
- Department of Gynaecology, Barking, Havering & Redbridge University Hospitals, Essex RM7 0AG, UK
- Asma Faruqi
- Department of Pathology, Barts Health NHS Trust, London E1 1FR, UK
- Giorgia Trevisan
- Department of Pathology, Barts Health NHS Trust, London E1 1FR, UK
- Laura Casey
- Department of Pathology, Barts Health NHS Trust, London E1 1FR, UK
- George J. Burghel
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Helene Schlecht
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Michael Bulman
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Philip Smith
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Naomi L. Bowers
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Rosa Legood
- Department of Health Services Research, Faculty of Public Health & Policy, London School of Hygiene & Tropical Medicine, London WC1H 9SH, UK
- Michelle Lockley
- Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Andrew Wallace
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Naveena Singh
- Department of Pathology, Barts Health NHS Trust, London E1 1FR, UK
- D. Gareth Evans
- Manchester Centre for Genomic Medicine, Saint Marys Hospital, Manchester M13 9WL, UK
- Ranjit Manchanda
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- DOI
- https://doi.org/10.3390/cancers13174344
- Journal volume & issue
-
Vol. 13,
no. 17
p. 4344
Abstract
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 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.
Keywords