Rapid whole-genome sequencing (rWGS) reduced the average time to a clinically interpretable genomic report from 42 days to 3 days in children with suspected or confirmed cancer, while identifying 95 percent of clinically actionable variants found across all testing methods.
In a study published in Nature Communications, scientists evaluated rWGS in 54 children with hematologic malignancies and solid tumors, including leukemia, lymphoma, tumors of the central nervous system, neuroblastoma, and Wilms tumor. Thirty-five patients were enrolled prospectively and 19 were assessed using archived samples.
The researchers compared rWGS with routine WGS provided by the National Health Service England Genomic Medicine Service and conventional molecular tests, including fluorescence in situ hybridization, targeted next-generation sequencing, and RNA fusion testing. Rapid WGS detected 147 of 155 clinically actionable germline and tumor variants identified by any method, compared with 138 of 155 for routine WGS. The eight variants missed by rWGS did not change diagnosis or management in the affected patients.
Speed was a key diagnostic advantage. Routine WGS took an average of 63 days for hematologic malignancies and 29 days for solid tumors in the study, compared with 3 days for both groups using rWGS. The rapid workflow shortened sample preparation and analysis in a number of ways, such as removing the need for fibroblast culture in patients with leukemia.
Among the 35 prospectively assessed patients, clinicians reported measurable improvements in care for 17 (49 percent). These included faster diagnosis and risk stratification, access to precision treatments, and avoidance of unnecessary investigations or therapies. In some cases, sequencing blood or other samples also provided sufficient diagnostic information to avoid more invasive procedures.
For one child with pancreatic cancer, a BRAF fusion was identified that enabled targeted treatment. Diagnosis of non-malignant conditions in two children presenting with soft tissue lesions prevented potentially harmful biopsy and treatment. Rapid sequencing also provided leukemia classification, measurable residual disease markers, risk information, and pharmacogenomic data from a single sample.
The findings suggest that shortening WGS turnaround time could move comprehensive genomic analysis from a supplementary investigation to an early diagnostic tool, making results available when initial treatment decisions are being made.
However, the researchers emphasize that this was a small, single-center, non-randomized study and was not designed to demonstrate clinical impact or cost savings. Larger multicenter studies are needed to establish reproducibility, cost-effectiveness, and scalability before rWGS could be implemented more widely. NHS England is now supporting a national trial of rWGS.
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