Moure et al., using patient-derived IDH1R132H/WT glioma cell lines and CRISPR-Cas9-mediated gene knockout, showed that abolishing of 2-HG production by genetic deletion of IDH alleles is not sufficient to completely reverse hypermethylation of all G-CIMP loci, despite a widespread pattern of demethylation and the formation of a G-CIMP-low-like phenotype [39]. This evidence concerns the gene IDH2 and central nervous system cancer.