Mutations in chromatin machinery and pediatric high-grade glioma

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Abstract
Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors.
Funding Information
  • The Matthew Larson Foundation for Pediatric Brain Tumors (ID0EOOAI5727)
  • Rally Foundation (ID0EB2AI5728)
  • Bear Necessities Pediatric Cancer Foundation (ID0EWHBI5729)
  • National Institutes of Health (ID0EJUBI5730, R01NS093079)
  • John McNicholas Pediatric Brain Tumor Foundation (ID0EABCI5731)
  • The Bagan Afmily Fellowship at the Neurosurgery Research and Education Foundation (ID0ETGCI5732)
  • The Cure Starts Now Foundation (ID0EMPCI5733)
  • Northwestern Memorial Faculty Founation (ID0EFYCI5734)
  • Northwestern University Clinical and Translational Sciences Institute Award (ID0E5ADI5735, UL1TR001422 and 1KL2TR001424-0)