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The landscape of structural variation in pediatric cancer - PubMed

4 hours ago
  • #RAG-mediated recombination
  • #structural variation
  • #pediatric cancer
  • Structural variants (SVs) account for over 60% of pediatric cancer driver variants.
  • Pediatric SV burden varies significantly across cancer types and is reduced compared to adult brain and solid tumors but comparable in hematological malignancies.
  • Top-ranked SV-disrupted genes are drivers in pediatric cancers and fragile sites in adult cancers.
  • Recurrent SV hotspots near RAG recombination signal sequences disrupt immune loci and driver genes in pediatric acute lymphoblastic leukemias.
  • Ten extracted SV signatures implicate RAG-mediated mutagenesis as a potential etiology for COSMIC SV7 in lymphoid cancers.
  • Clustering of samples from 13 patients reveals ongoing evolutionary contributions of SVs to intra-tumor heterogeneity and driver selection.
  • The study expands the known scope of RAG-mediated mutagenesis and provides a curated SV dataset for future research and clinical testing.