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. Whole-genome sequencing (WGS) can provide important benefits to childhood cancer patients, but clinical WGS workflows typically take weeks. Here, the authors evaluate the feasibility and efficacy of a rapid WGS research workflow with streamlined bioinformatics, reducing the mean turnaround time from 42 to 3 days without sacrificing the detection of clinically actionable variants.