Diagnostic yield of cancer predisposition in a nationwide prospective childhood acute leukemia cohort.

Whole-genome sequencing identifies pathogenic germline alterations in 7.7% of childhood leukemia cases, enabling tailored clinical management in a nationwide cohort.

• Why it matters: Detecting genetic predispositions in childhood leukemia is crucial for personalized treatment and surveillance, yet the diagnostic utility of comprehensive genomic approaches remains uncertain.
• What they did: A prospective study of 181 children used systematic phenotyping, germline WGS of 189 genes, tumor sequencing, and trio-WGS in high-suspicion families to identify genetic predispositions.
• The result: Nine patients had pathogenic germline alterations, with six previously unrecognized, leading to personalized surveillance and treatment changes, demonstrating the approach's clinical actionability despite modest diagnostic yield.