Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas

Cancer Cell. 2020 Apr 13;37(4):569-583.e5. doi: 10.1016/j.ccell.2020.03.011.


Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.

Keywords: RAS/MAPK pathway; brain tumor; low-grade glioma; molecular diagnostics; neurooncology; pediatric; risk stratification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / classification
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Copy Number Variations*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Rearrangement*
  • Glioma / classification
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitogen-Activated Protein Kinases / genetics
  • Mutation*
  • Neurofibromin 1 / genetics
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • ras Proteins / genetics


  • BRAF-KIAA1549 fusion protein, human
  • Biomarkers, Tumor
  • NF1 protein, human
  • Neurofibromin 1
  • Oncogene Proteins, Fusion
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases
  • ras Proteins