In line with the current finding that 2-HG production, but not dominant negative function, is conferred by glioma-derived NADP+-dependent IDH mutations [39], coupled with their role to block the histone demethylation and associate with CIMP [32], we could speculate that in the homozygous R132H carrier the extent of methylation will be greatly increased compared to the heterozygote. This evidence concerns the gene IDH1 and central nervous system cancer.