High levels of D-2HG induce histone and DNA hypermethylation through competitive inhibition of histone and DNA demethylases, thereby blocking cell differentiation and promoting neural stem-like phenotype [17,18,19]; however, neural stem-cell marker genes such as NES and PROM1 are generally downregulated in IDH-mutant glioma [20]. This evidence concerns the gene IDH2 and glioma.