IDH2 and glioma: Through an altered substrate specificity, IDH mutations give rise to metabolic alterations, including an increase in production of 2-hydroxyglutarate (2-HG) which can inhibit histone demethylation and induces a glioma hypermethylation phenotype (glioma CpG island methylated phenotype or G-CIMP) [45, 75, 116].