Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the…

• PB
  Pediatric Brain Tumor Foundation
• CS
  Cure Starts Now Foundation
• CR
  Cancer Research UK

  Awards: C13468/A23536, C13468/A13982
• CW
  CHILDREN with CANCER UK
• BT
  Brain Tumour Charity
• NI
  National Institutes of Health

  Awards: R01NS091620, R01NS085336