| First Author | Cairns RA | Year | 2013 |
| Journal | Cancer Discov | Volume | 3 |
| Issue | 7 | Pages | 730-41 |
| PubMed ID | 23796461 | Mgi Jnum | J:204215 |
| Mgi Id | MGI:5529852 | Doi | 10.1158/2159-8290.CD-13-0083 |
| Citation | Cairns RA, et al. (2013) Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities. Cancer Discov 3(7):730-41 |
| abstractText | Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing mutant IDH, D2HG concentrations are highly elevated. D2HG may act as an "oncometabolite" by inhibiting a class of alpha-KG-dependent enzymes involved in epigenetic regulation, collagen synthesis, and cell signaling. Knock-in mouse models of IDH1 mutations have shed light on these mechanisms and will provide valuable animal models for further investigation. |
