Brain Tumors of Glial Origin

Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.