Abstract
Background: Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally.
Methods: Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value.
Results: Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36).
Conclusion: Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.
| Original language | English |
|---|---|
| Pages (from-to) | 137-144 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 127 |
| Issue number | 1 |
| Early online date | 22 Apr 2022 |
| DOIs | |
| Publication status | Published - 1 Jul 2022 |
Bibliographical note
Funding Information:We dedicate this work to the memory of Dr Johannes Visser, Consultant Paediatric Oncologist, Cambridge University Hospitals NHS Foundation Trust, whose kind, caring, wise and compassionate nature offered so much to improve outcomes for children affected by cancer.This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. Decision support software, Base Space Variant Interpreter, was provided and supported by Illumina. Findings were analysed, confirmed and clinically reviewed by Clinical Genetics and the Paediatric Haematology and Oncology Departments at the Cambridge University Hospitals NHS Foundation Trust. TSJ is grateful for funding from the Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children’s Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the National Institute of Health Research via the Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health, made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. We would like to acknowledge the work of Claire Beyeler in the recruitment of patients into this study and Professor Lucy Raymond who was the clinical lead for the East of England GMC. We also gratefully acknowledge the members of the Genomics England Research Consortium, listed below, for providing the detailed data and infrastructures to enable clinical cancer WGS. Ambrose J. C., Arumugam P., Bevers R., Bleda M., Boardman-Pretty F., Boustred C. R., Brittain H., Caulfield M. J., Chan G. C., Fowler T., Giess A., Hamblin A., Henderson S., Hubbard T. J. P., Jackson R., Jones L. J., Kasperaviciute D., Kayikci M., Kousathanas A., Lahnstein L., Leigh S. E. A., Leong I. U. S., Lopez F. J., Maleady-Crowe F., McEntagart M., Minneci F., Moutsianas L., Mueller M., Murugaesu N., Need A. C., O‘Donovan P., Odhams C. A., Patch C., Perez-Gil D., Pereira M. B., Pullinger J., Rahim T., Rendon A., Rogers T., Savage K., Sawant K., Scott R. H., Siddiq A., Sieghart A., Smith S. C., Sosinsky A., Stuckey A., Tanguy M, Taylor Tavares A. L, Thomas E. R. A., Thompson S. R., Tucci A., Welland M. J., Williams E., Witkowska K., Wood S. M.
SB receives a personal fellowship from the Wellcome Trust (110104/Z/15/Z).
Publisher Copyright:
© 2022, The Author(s).
ASJC Scopus subject areas
- Oncology
- Cancer Research
