title: Mutations in chromatin machinery and pediatric high-grade glioma.
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.
authors.affiliation: Department of Pediatrics-Hematology, Oncology, Neuro-Oncology and Stem Cell Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Rishi R
authors.initials: RR
authors.lastname: Lulla
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Amanda Muhs
authors.identifier: 0000-0002-4913-2771
authors.initials: AM
authors.lastname: Saratsis
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D060787:Neoplasm Grading; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D006657:Histones
keywords: DIPG; G34V/R; GSKJ4; Histone mutation; JMJD3; K27M; PRC2; demethylase; methyltransferase; pediatric high-grade glioma