Given the fact that IDH mutations are early events (“founder mutation”) in LGG development [46], it stands to reason that the early gain of IDH mutations prevents glioma from acquiring additional malignant traits seen in IDH-wildtype glioma, whereas functional loss of IDH mutations, such as the loss of DNA hypermethylation in the newly identified IDH-mutant glioma subtype [39], results in unfavorable clinical outcome. The gene discussed is IDH2; the disease is glioma.