ArticleJCO precision oncology2026
Germline Whole-Genome Sequencing in Early-Onset Pediatric Solid Tumors Implicates Novel Risk Factors.
Article in JCO precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- The Role of Germline Transposable Element Insertions in Pediatric Cancer Predisposition.Cancer research communications · 2026Article
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15 authors.
Funding
Abstract
purposeMany children with very early-onset solid tumors remain without an identified germline risk factor after negative panel testing. Whole-genome sequencing (WGS) enables detection of large structural variants (SVs) and rare loss-of-function variants in highly constrained genes that are not routinely captured by standard clinical assays. The additional yield and spectrum of germline findings identified by WGS in this population remain incompletely defined.
methodsWe conducted a retrospective cohort study of children with very early-onset solid or brain tumors evaluated at a tertiary cancer genetic risk clinic with clinically guided germline panel testing. Germline WGS was performed on blood-derived DNA. Analyses focused on pathogenic or likely pathogenic variants in established cancer predisposition genes (CPGs), large SVs (>1,000,000 bp), aneuploidies, and loss-of-function variants in highly constrained genes.
resultsOne hundred thirty-two patients were included, with median (IQR) age at diagnosis of 1.7 (0.8-3.2) years. Panel testing identified pathogenic CPG variants in 27 of 132 patients (20%). WGS recapitulated panel findings and identified nine additional putative pathogenic variants, increasing yield to 27%. Eight patients (6%) harbored large germline SVs or aneuploidies, including five events not previously recognized. Rare loss-of-function variants in highly constrained genes were identified in 46 patients (35%), many involving pathways relevant to cancer development. Overall, 66 of 132 patients (50%) carried at least one rare germline variant of potential pathogenic relevance.
conclusionIn children with very early-onset solid tumors, germline WGS increased detection of potentially pathogenic variants, including novel structural and constrained-gene alterations. These findings support broader consideration of germline WGS in early-onset solid tumors to refine genetic risk assessment and enable discovery of novel susceptibility mechanisms.
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