Germline Whole-Genome Sequencing in Early-Onset Pediatric Solid Tumors Implicates Structural Variants in Cancer Risk

Germline WGS in pediatric oncology after negative panel testing, identification of SVs and rare LOF variants not captured by panels

Children with very early-onset solid tumors and negative genetic panel testing are explored by germline WGS. WGS detects large structural variants (SVs) and rare loss-of-function variants in highly constrained genes, invisible to standard multi-gene panels. A significant proportion of patients obtain a genetic predisposition diagnosis, with implications for surveillance monitoring and family screening. This study supports integrating WGS as second-tier oncogenetics workup in pediatrics.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Germline WGS in pediatric oncology represents the logical extension of diagnostic WGS in constitutional genetics. Identification of pathogenic SVs after negative panel clearly justifies a WGS second-tier approach for very early-onset tumors — especially when no hotspot mutation is found.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 7/10