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.

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.