Journal Article

Benefits for children with suspected cancer from routine whole-genome sequencing

Kennedy, Jonathan, Coleman, Nicholas, Samarasinghe, Sujith, Rao, Anupama, Barnard, Gemma, Tarpey, Patrick, McDerra, Joanna, Dryden, Caryl, Nagrecha, Rajvi, Tadross, John A., Allinson, Kieren, Trayers, Claire, Bartram, Jack, Cheng, Danny, Watkins, James, Cano-Flanagan, Julian, Ghorashian, Sara, May, Phillippa, Behjati, Sam, Clinch, Yasmin, Griffin, Blanche, Ajithkumar, Thankamma, Burke, G. A. Amos, Pavasovic, Vesna, Roberts, Thomas, O’Connor, David, Leiter, Sarah M., Chalker, Jane, Vedi, Aditi, Chitty, Lyn S., Armstrong, Ruth, Ancliff, Phil, Vora, Ajay, Trotman, Jamie, Bailey, Shivani, Stasevich, Iryna, Hodder, Angus, Hubank, Michael, Nicholson, James, Ahmed, Munaza, Murray, Matthew J., Horan, Gail, Bowdin, Sarah, Quaegebeur, Annelies, Hook, Catherine E., Addy, Dilys, Burns, Charlotte

2024

Overview

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units ( n  = 152 from a hematology center, n  = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test ( n  = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care. In a cohort of 281 children with diagnosed or suspected cancer presenting to the NHS, implementing routine whole-genome sequencing provided clinical benefit in 29% of cases and led to change in management in 7% of patients.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/212 / 631/67/69 / 692/308/2056 / 692/700/1720 / Adolescent / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Child / Child, Preschool / Children / Disease management / Female / Gene sequencing / Genetic Testing - methods / Genome, Human - genetics / Genomes / Genomics / Genomics - methods / Humans / Infant / Infant, Newborn / Infectious Diseases / Information management / Male / Metabolic Diseases / Molecular Medicine / Neoplasms - diagnosis / Neoplasms - genetics / Neoplasms - therapy / Neurosciences / Patients / Risk groups / Solid tumors / Tumors / Whole Genome Sequencing