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Krebs cycle to DNA methylation. IDH1/2 wild-type enzymes convert isocitrate to α-ketoglutarate (αKG), a TET2 substrate. IDH1/2 mutations result in neomorphic enzymes converting αKG to 2-hydroxyglutarate (2HG) which is an oncometabolite. 2HG can compromise the function of TET2. In addition, TET2 and DNMT3A genes are involved in epigenetic transcriptional regulation by maintaining the DNA methylation during DNA replication and cell division.
