TET2

Summary

Gene Symbol: TET2
Description: tet methylcytosine dioxygenase 2
Alias: KIAA1546, MDS, methylcytosine dioxygenase TET2, tet oncogene family member 2
Species: human
Products:     TET2

Top Publications

  1. Zhang Q, Liu X, Gao W, Li P, Hou J, Li J, et al. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked β-N-acetylglucosamine transferase (OGT). J Biol Chem. 2014;289:5986-96 pubmed publisher
    ..Although TET1 and TET2 also interact with and can be O-GlcNAcylated by OGT, neither their subcellular localization nor their enzymatic ..
  2. Saint Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009;114:1628-32 pubmed publisher
    ..A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations ..
  3. Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24:1128-38 pubmed publisher
    ..a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), ..
  4. Abdel Wahab O. Genetics of the myeloproliferative neoplasms. Curr Opin Hematol. 2011;18:117-23 pubmed publisher
    ..mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1...
  5. Bejar R, Lord A, Stevenson K, Bar Natan M, P rez Ladaga A, Zaneveld J, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124:2705-12 pubmed publisher
    ..The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = ...
  6. Jankowska A, Szpurka H, Tiu R, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113:6403-10 pubmed publisher
    ..We then investigated genes in the commonly affected area for mutations. When we sequenced TET2, we found homozygous and hemizygous mutations...
  7. Deplus R, Delatte B, Schwinn M, Defrance M, Mendez J, Murphy N, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32:645-55 pubmed publisher
    ..has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited...
  8. Pronier E, Almire C, Mokrani H, Vasanthakumar A, Simon A, da Costa Reis Monte Mor B, et al. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood. 2011;118:2551-5 pubmed publisher
    b>TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms...
  9. Figueroa M, Abdel Wahab O, Lu C, Ward P, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18:553-67 pubmed publisher
    ..In the AML cohort, IDH1/2 mutations were mutually exclusive with mutations in the α-ketoglutarate-dependent enzyme TET2, and TET2 loss-of-function mutations were associated with similar epigenetic defects as IDH1/2 mutants...
  10. Smith A, Mohamedali A, Kulasekararaj A, Lim Z, Gaken J, Lea N, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood. 2010;116:3923-32 pubmed publisher
    Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear...

Detail Information

Publications62

  1. Zhang Q, Liu X, Gao W, Li P, Hou J, Li J, et al. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked β-N-acetylglucosamine transferase (OGT). J Biol Chem. 2014;289:5986-96 pubmed publisher
    ..Although TET1 and TET2 also interact with and can be O-GlcNAcylated by OGT, neither their subcellular localization nor their enzymatic ..
  2. Saint Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009;114:1628-32 pubmed publisher
    ..A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations ..
  3. Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24:1128-38 pubmed publisher
    ..a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), ..
  4. Abdel Wahab O. Genetics of the myeloproliferative neoplasms. Curr Opin Hematol. 2011;18:117-23 pubmed publisher
    ..mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1...
  5. Bejar R, Lord A, Stevenson K, Bar Natan M, P rez Ladaga A, Zaneveld J, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124:2705-12 pubmed publisher
    ..The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = ...
  6. Jankowska A, Szpurka H, Tiu R, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113:6403-10 pubmed publisher
    ..We then investigated genes in the commonly affected area for mutations. When we sequenced TET2, we found homozygous and hemizygous mutations...
  7. Deplus R, Delatte B, Schwinn M, Defrance M, Mendez J, Murphy N, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32:645-55 pubmed publisher
    ..has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited...
  8. Pronier E, Almire C, Mokrani H, Vasanthakumar A, Simon A, da Costa Reis Monte Mor B, et al. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood. 2011;118:2551-5 pubmed publisher
    b>TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms...
  9. Figueroa M, Abdel Wahab O, Lu C, Ward P, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18:553-67 pubmed publisher
    ..In the AML cohort, IDH1/2 mutations were mutually exclusive with mutations in the α-ketoglutarate-dependent enzyme TET2, and TET2 loss-of-function mutations were associated with similar epigenetic defects as IDH1/2 mutants...
  10. Smith A, Mohamedali A, Kulasekararaj A, Lim Z, Gaken J, Lea N, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood. 2010;116:3923-32 pubmed publisher
    Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear...
  11. Schaub F, Looser R, Li S, Hao Shen H, Lehmann T, Tichelli A, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood. 2010;115:2003-7 pubmed publisher
    Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F...
  12. Nguyen Khac F, Lesty C, Eclache V, Couronné L, Kosmider O, Andrieux J, et al. Chromosomal abnormalities in transformed Ph-negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations. Genes Chromosomes Cancer. 2010;49:919-27 pubmed publisher
    ..JAK2V617F and TET2 mutations were searched for in 40 and 32 patients, respectively. Significantly more -7/del(7q) (P = 0...
  13. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360:2289-301 pubmed publisher
    ..The coding sequence of this gene, TET2, was determined in 320 patients...
  14. Flach J, Dicker F, Schnittger S, Kohlmann A, Haferlach T, Haferlach C. Mutations of JAK2 and TET2, but not CBL are detectable in a high portion of patients with refractory anemia with ring sideroblasts and thrombocytosis. Haematologica. 2010;95:518-9 pubmed publisher
  15. Hu L, Li Z, Cheng J, Rao Q, Gong W, Liu M, et al. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell. 2013;155:1545-55 pubmed publisher
    ..Mutations of TET2 are frequently observed in myeloid malignance...
  16. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17-30 pubmed publisher
    ..Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations. ..
  17. Lorsbach R, Moore J, Mathew S, Raimondi S, Mukatira S, Downing J. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia. 2003;17:637-41 pubmed
  18. Chen Q, Chen Y, Bian C, Fujiki R, Yu X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature. 2013;493:561-4 pubmed publisher
    Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine and regulate gene transcription...
  19. Kim Y, Pierscianek D, Mittelbronn M, Vital A, Mariani L, Hasselblatt M, et al. TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations. J Clin Pathol. 2011;64:850-2 pubmed publisher
    Miscoding mutations of the TET2 gene, which encodes the α-ketoglutarate-dependent enzyme that catalyses the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, thus producing DNA demethylation, have been detected in 10-25% of ..
  20. Couronné L, Lippert E, Andrieux J, Kosmider O, Radford Weiss I, Penther D, et al. Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia. 2010;24:201-3 pubmed publisher
  21. Gelsi Boyer V, Trouplin V, Roquain J, Adélaïde J, Carbuccia N, Esterni B, et al. ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. Br J Haematol. 2010;151:365-75 pubmed publisher
    ..and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1...
  22. Soucie E, Hanssens K, Mercher T, Georgin Lavialle S, Damaj G, Livideanu C, et al. In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells. Blood. 2012;120:4846-9 pubmed publisher
    ..number of aggressive and nonaggressive cases of systemic mastocytosis, that in contrast to the oncogenic KITD816V, TET2 mutation statistically associates with aggressive forms of the disease...
  23. Traina F, Visconte V, Jankowska A, Makishima H, O Keefe C, Elson P, et al. Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. PLoS ONE. 2012;7:e43090 pubmed publisher
    ..areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family...
  24. Muramatsu H, Makishima H, Jankowska A, Cazzolli H, O Keefe C, Yoshida N, et al. Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia. Blood. 2010;115:1969-75 pubmed publisher
    ..In total, c-Cbl mutations were detected in 5 (10%) of 49 patients. No mutations were identified in Cbl-b and TET2. c-Cbl and RAS pathway mutations were mutually exclusive...
  25. Carbuccia N, Murati A, Trouplin V, Brecqueville M, Adelaide J, Rey J, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia. 2009;23:2183-6 pubmed publisher
  26. Rakoczy J, Padmanabhan N, Krzak A, Kieckbusch J, Cindrova Davies T, Watson E. Dynamic expression of TET1, TET2, and TET3 dioxygenases in mouse and human placentas throughout gestation. Placenta. 2017;59:46-56 pubmed publisher
    ..Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider ..
  27. Solary E, Bernard O, Tefferi A, Fuks F, Vainchenker W. The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. Leukemia. 2014;28:485-96 pubmed publisher
    Ten-Eleven Translocation-2 (TET2) inactivation through loss-of-function mutation, deletion and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutation is a common event in myeloid and lymphoid malignancies...
  28. Guilhamon P, Eskandarpour M, Halai D, Wilson G, Feber A, Teschendorff A, et al. Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2. Nat Commun. 2013;4:2166 pubmed publisher
    ..and using chromatin immunoprecipitation and western blotting, we identify the transcription factor EBF1 (early B-cell factor 1) as an interaction partner for TET2, suggesting a sequence-specific mechanism for regulating DNA methylation.
  29. Chim C, Wan T, Fung T, Wong K. Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms. J Clin Pathol. 2010;63:942-6 pubmed publisher
    A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the pathogenesis or leukaemic transformation of myeloproliferative neoplasm...
  30. Couronné L, Bastard C, Bernard O. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366:95-6 pubmed publisher
  31. Garcia Gomez A, Li T, Kerick M, Català Moll F, Comet N, Rodriguez Ubreva J, et al. TET2- and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells. Nucleic Acids Res. 2017;45:10002-10017 pubmed publisher
    ..b>TET2, a methylcytosine dioxygenase highly expressed in these cells and frequently mutated in myeloid leukemias, may be a ..
  32. Makishima H. Sequential acquisition of mutations in myelodysplastic syndromes. Rinsho Ketsueki. 2017;58:1828-1837 pubmed publisher
    ..In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological ..
  33. Schuler E, Frank F, Hildebrandt B, Betz B, Strupp C, Rudelius M, et al. Myelodysplastic syndromes without peripheral monocytosis but with evidence of marrow monocytosis share clinical and molecular characteristics with CMML. Leuk Res. 2017;65:1-4 pubmed publisher
    ..Twenty patients of each group were screened with regard to ASXL1, TET2, RUNX1, SETBP1, NRAS, and SRSF2 using Illumina myeloid panel...
  34. Wakita S, Yamaguchi H, Omori I, Terada K, Ueda T, Manabe E, et al. Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia. Leukemia. 2013;27:1044-52 pubmed publisher
    ..1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease ..
  35. Schönberger K, Cabezas Wallscheid N. Vitamin C: C-ing a New Way to Fight Leukemia. Cell Stem Cell. 2017;21:561-563 pubmed publisher
    ..Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity.
  36. Alayed K, Patel K, Konoplev S, Singh R, Routbort M, Reddy N, et al. TET2 mutations, myelodysplastic features, and a distinct immunoprofile characterize blastic plasmacytoid dendritic cell neoplasm in the bone marrow. Am J Hematol. 2013;88:1055-61 pubmed publisher
    ..Targeted next-generation sequencing performed on five BPDCN cases identified TET2 (ten eleven translocation 2) mutations and no other AML-associated mutations...