Abstract Whole genome sequencing (WGS) improves childhood cancer diagnosis, enabling precision treatment. However, timely clinical decisions are made within days, while WGS clinical reports using current technologies and workflows, can exceed 6 weeks. Here we report an ‘Ultra-fast WGS (UF-WGS)’ workflow, providing rapid and acurate molecular profiling of childhood malignancies. In 54 children with suspected or confirmed cancer, UF-WGS reduced turnaround time from 37 to 3 days. It captured 95% of clinically actionable variants found by conventional methods, and identified 19 additional actionable variants. UF-WGS led to demonstrable improvements in care for 51% of prospective patients, including avoidance of over-medicalisation and support for timely precision therapy. UF-WGS was feasible across diverse tumour types and sample sources, with additional technical advantages in variant detection and workflow simplicity. These findings indicate UF-WGS can significantly improve the management of paediatric haematology/oncology patients, specifically through precision diagnosis, risk stratification and molecularly informed treatment escalation/de-escalation.
Rowitch et al. (Fri,) studied this question.