title: Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma.
abstract: Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1-mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.
authors.affiliation: Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children;
authors.forename: Sameer
authors.initials: S
authors.lastname: Agnihotri
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Gelareh
authors.initials: G
authors.lastname: Zadeh
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D007521:Isocitrate Dehydrogenase
keywords: 2HG = 2-hydroxyglutarate; CDK = cyclin-dependent kinase; CIMP = CpG island hypermethylator phenotype; DNMT = DNA methyltransferase; EGFR = epidermal growth factor receptor; GBM = glioblastoma; HIF-1α = hypoxia-inducible factor 1α; IDH = isocitrate dehydrogenase; IDH1; MES = mesenchymal; NF-κB = nuclear factor κB; PDGFRα = platelet-derived growth factor receptor–α; PDK = pyruvate dehydrogenase kinase; PN = proneural; TCGA = the Cancer Genome Atlas; TET = ten-eleven translocation; glioblastoma; tumor metabolism; α-KG = α-ketoglutarate