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

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.

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