Objective:

To assess the diagnostic performance and turnaround time of rapid whole-genome sequencing (rWGS) in children with suspected or confirmed cancer.

Approach:

• Study population: Researchers evaluated 54 children with hematologic malignancies or solid tumors; 35 were enrolled prospectively and 19 were assessed using archived samples.
• Comparisons: rWGS was compared with routine NHS England WGS and conventional molecular tests, including FISH, targeted next-generation sequencing, and RNA fusion testing.

Key Findings:

• Average time to a clinically interpretable report was 3 days with rWGS, compared with 42 days overall for routine WGS; routine WGS averaged 63 days for hematologic malignancies and 29 days for solid tumors.
• rWGS detected 147 of 155 clinically actionable variants identified across all methods, compared with 138 of 155 for routine WGS. The eight variants missed by rWGS did not change diagnosis or management in the affected patients.
• Clinicians reported measurable care improvements for 17 of 35 prospectively assessed patients (49%), including faster diagnosis or risk stratification, access to precision treatments, and avoidance of some investigations or therapies.
• Examples included identifying a BRAF fusion that enabled targeted treatment and diagnosing non-malignant conditions in two children with soft tissue lesions, avoiding potentially harmful biopsy and treatment.

Interpretation:

The study authors suggest that faster WGS reporting could make comprehensive genomic analysis available earlier in diagnostic care, when initial treatment decisions are being made.

Limitations:

• The study was small, single-center, and non-randomized.
• It was not designed to demonstrate clinical impact or cost savings.
• The authors state that larger multicenter studies are needed to assess reproducibility, cost-effectiveness, and scalability.

Conclusion:

NHS England is supporting a national trial of rWGS.

Sources:

• Nature Communications study, as described in the provided article context