Figure 2. DNA demethylation dynamics in human cancers.

(A) Role of IDH1 in shaping the cancer methylome. WT IDH1 converts isocitrate to α-KG, but the mutant IDH1^R132H enzyme catalyzes the conversion α-KG to 2-HG, which inhibits TET-mediated DNA demethylation. This mechanism is proposed to explain DNA hypermethylation in IDH1- and TET-mutated cancers. (B) Proposed mechanism of DNA demethylation by the TET family of DNA demethylases, followed by thymine-DNA glycosylase (TDG) base excision repair, resulting in unmethylated cytosines.