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Clinical Impact of Ultra-Fast Whole Genome Sequencing in Paediatric Haematology-Oncology Practice

por Aditi Vedi, Jamie Trotman, Joao ML Dias, Martina Mijuskovic, Sera Choi, Laura Kingham, A Rachel Moore, Sarah M Leiter, Rowena Guermech, Amanda Semerene, Aviva Grisby, Sophie Wool, Victoria Joslin, Arunthethy Mahendrayogam, Jonathan Abrams, Michael Gattens, Esther Blanco, Emmy L Dickens, Charlotte Burns, Matthew J Murray, John A Tadross, Claire Trayers, Catherine E. Hook, Jennifer Becq, Taksina Newington, Ivana Armogida, Zoya Kingsbury, Pascal Grobecker, Ines Vitoriano, Mitch Bekritsky, Jacqui Weir, Louise Fraser, Mark Ross, David Bentley, Matthew Cullen, Sam Behjati, Sean Humphray, David Rowitch y Patrick Tarpey

Publicada: 2 de septiembre de 2025
Servidor: medRxiv
DOI: 10.1101/2025.08.29.25334714

Background

Whole Genome Sequencing (WGS) enhances paediatric cancer diagnosis and management compared with standard molecular assays. However, its clinical utility could be further improved by reducing the National Health Service England (NHSE) turnaround times (TAT).

Methods

We evaluated an ‘Ultra-Fast WGS’ (UF-WGS) workflow in a tertiary UK paediatric haematology-oncology unit. Children with suspected or confirmed cancer were recruited over two years (2023-2025), and their tumour, bone marrow and/or blood samples were sequenced on the UF-WGS workflow. All patients underwent concurrent NHSE Genomic Medicine Service (GMS) WGS, serving as the validation benchmark.

Results

A total of 54 patients were recruited at diagnosis or relapse. UF-WGS reduced TAT to a mean of 3 days from sample collection, compared with 37 days for GMS-WGS. UF-WGS recalled 95% (143/151) of all clinically actionable somatic and germline variants found by standard NHS GMS-WGS testing. UF-WGS detected an additional 19 clinically actionable variants not found by GMS-WGS. Differences between the two workflows were attributable to tumour heterogeneity in some cases, and low variant allele frequency of those variants identified discrepantly.

Additionally, in 18/35 (51%) prospective cases, UF-WGS enabled demonstrable improvements in care. Clinicians independently judged that 9/19 (47%) of the retrospective cases would have clinically benefited from real-time UF-WGS. UF-WGS provided additional flowcell proximity data, which illustrated the potential to positively impact clinical care.

Conclusions

This study indicates the feasibility and utility of UF-WGS and shows added benefits for the clinical management of paediatric cancers, with wider implications beyond this patient group.

Trial Registration

22/WA/0336, NCT 07201038 ( clinicaltrials.gov )

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