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. The gene discussed is IDH2; the disease is central nervous system cancer.