The mutant forms of IDH acquire a neomorphic activity and instead convert isocitrate to D-2-hydroxyglutarate, a so-called “oncometabolite” that builds to a very high level in tumor cells and interferes with several cellular processes, ultimately resulting in changes to DNA and histone methylation patterns that alter gene expression by establishing a glioma CpG island methylator phenotype (G-CIMP) [43, 44]. Here, IDH2 is linked to glioma.