Rapid Whole Genome Sequencing Enhances Pediatric Cancer Diagnosis
Abstract Whole-genome sequencing (WGS) has been shown to improve diagnosis beyond standard-of-care genetic tests and guide precision treatment for childhood cancer. While WGS is now offered for children with suspected cancer in England, clinical workflows typically return results after several weeks whereas clinical decisions are often required within days. Here we evaluate feasibility and efficacy of a rapid WGS (rWGS) research workflow with streamlined bioinformatics to deliver clinical genomic findings (NCT07201038, Active, not recruiting). In 54 children with suspected or confirmed malignancy, rWGS reduces mean end-to-end turnaround time from 42 to 3 days, whilst increase variant detection rate. Whereby rWGS detected 147 of 155 (95%) clinically actionable variants identified in the cohort, standard of care testing detected 138 of 155 (89%) variants. In a subset of 35 patients assessed prospectively, clinicians report that in 17 (49%), rWGS either (i) facilitates faster access to targeted therapy and risk stratification, or (ii) avoids unnecessary investigations and treatment escalation. These findings indicate feasibility and suggest clinical utility of rWGS when deployed as a first line diagnostic test in pediatric oncology.
Authors
- Aditi Vedi (ORCID: https://orcid.org/0000-0001-6761-6510)
- Jack Luke Bartram (ORCID: https://orcid.org/0000-0003-1573-2506)
- Pascal Grobecker (ORCID: https://orcid.org/0009-0001-8339-4775)
- Inês Vitoriano
- Arunthethy Mahendrayogam
- Mitchell A. Bekritsky (ORCID: https://orcid.org/0000-0003-1420-1172)
- Sean Humphray
- Claire Trayers (ORCID: https://orcid.org/0000-0003-0236-6041)
- Esther Blanco
- Zoya Kingsbury
- Louise J. Fraser (ORCID: https://orcid.org/0000-0001-9709-6827)
- David H. Rowitch (ORCID: https://orcid.org/0000-0002-0079-0060)
- Patrick S. Tarpey (ORCID: https://orcid.org/0000-0002-2042-4543)
- Sophie V. Wool
- Jacqueline Weir
- Sarah M. Leiter (ORCID: https://orcid.org/0000-0001-8321-3260)
- Sam Behjati (ORCID: https://orcid.org/0000-0002-6600-7665)
- Michael Gattens
- Ivana Armogida
- Martina Mijušković
- João M.L. Dias (ORCID: https://orcid.org/0000-0002-8451-3537)
- Jamie Trotman (ORCID: https://orcid.org/0000-0002-6246-4121)
- Jennifer Becq
- Matthew Jonathan Murray (ORCID: https://orcid.org/0000-0002-4480-1147)
- John A. Tadross (ORCID: https://orcid.org/0000-0002-8424-1252)
- Taksina Newington
- Mark T. Ross (ORCID: https://orcid.org/0000-0001-7851-1167)
- Aviva Grisby
- David Bentley
- Jonathan Abrams (ORCID: https://orcid.org/0000-0002-4044-6969)
- Matthew J. Cullen
- Emmy Dickens
- C. Elizabeth Hook (ORCID: https://orcid.org/0000-0002-0450-7656)
- Charlotte Burns (ORCID: https://orcid.org/0000-0001-5139-2444)
- Rowena Guermech
- Amanda Semerene
- Victoria Joslin
- Laura Kingham
- Sera Choi
- Rachel A. Moore
Institutions
- Cedars-Sinai Medical Center (US)
- Illumina (United States) (US)
- University of Cambridge (GB)
- Great Ormond Street Hospital (GB)
- Hospital for Sick Children (CA)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- Illumina (United Kingdom) (GB)
- Wellcome/MRC Institute of Metabolic Science (GB)
- MRC Metabolic Diseases Unit
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-06
- DOI
- https://doi.org/10.1038/s41467-026-77918-x
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00