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

  • 1 Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • 2 Wellcome Sanger Institute, Hinxton, UK.
  • 3 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 4 Department of Paediatrics, University of Cambridge, Cambridge, UK.
  • 5 North Thames Genomic Laboratory Hub, London, UK.
  • 6 Department of Pathology, University of Cambridge, Cambridge, UK.
  • 7 UCL Great Ormond Street Institute of Child Health, London, UK.
  • 8 The Institute of Cancer Research, London, UK.
  • 9 UCL Cancer Institute, University College London, London, UK.
  • 10 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • 11 East Genomics Laboratory Hub, Cambridge, UK.
  • 12 MRC Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • 13 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. mjm16@cam.ac.uk.
  • 14 Department of Pathology, University of Cambridge, Cambridge, UK. mjm16@cam.ac.uk.
  • 15 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. lizhook@nhs.net.
  • 16 Department of Pathology, University of Cambridge, Cambridge, UK. lizhook@nhs.net.
  • 17 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. patrick.tarpey1@nhs.net.
  • 18 East Genomics Laboratory Hub, Cambridge, UK. patrick.tarpey1@nhs.net.
  • 19 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. a.vedi@nhs.net.
  • 20 Department of Paediatrics, University of Cambridge, Cambridge, UK. a.vedi@nhs.net.
  • 21 Great Ormond Street Hospital NHS Foundation Trust, London, UK. jack.bartram@gosh.nhs.uk.
  • 22 North Thames Genomic Laboratory Hub, London, UK. jack.bartram@gosh.nhs.uk.
  • 23 Wellcome Sanger Institute, Hinxton, UK. sb31@sanger.ac.uk.
  • 24 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. sb31@sanger.ac.uk.
  • 25 Department of Paediatrics, University of Cambridge, Cambridge, UK. sb31@sanger.ac.uk.
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July 2, 2024

Abstract

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.

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