5-hydroxymethylcytosine in cancer: Significance in diagnosis and therapy

Cancer Genetics

Volumn 208, Issue 5, 2015, Pages 167-177

  Vasanthakumar, Aparna ^a   Godley, Lucy A ^a  

^a SECTION OF HEMATOLOGY ONCOLOGY   (United States)

Author keywords

5 hydroxymethylcytosine; 5 methylcytosine; DNMT; TET

Indexed keywords

5 CARBOXYLCYTOSINE; 5 FORMYLCYTOSINE; 5 HYDROXYMETHYLCYTOSINE; 5 METHYLCYTOSINE; DIOXYGENASE; DNA (CYTOSINE 5) METHYLTRANSFERASE; DNA GLYCOSYLTRANSFERASE; DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 3A; ISOCITRATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE (NAD); ISOCITRATE DEHYDROGENASE (NADP); ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; JANUS KINASE 2; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; S ADENOSYLMETHIONINE; TEMOZOLOMIDE; TET METHYLCYTOSINE DIOXYGENASE; UNCLASSIFIED DRUG; 5-HYDROXYMETHYLCYTOSINE; CYTOSINE; DNA BINDING PROTEIN; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE 2, HUMAN; ONCOPROTEIN; TET2 PROTEIN, HUMAN;

ACUTE LYMPHOBLASTIC LEUKEMIA; CANCER CELL; CHRONIC MYELOMONOCYTIC LEUKEMIA; CITRIC ACID CYCLE; DNA HELIX; DNA METHYLATION; DNA STRUCTURE; DOWN REGULATION; ELECTROSPRAY MASS SPECTROMETRY; EPIGENETICS; GENE EXPRESSION REGULATION; GLIOBLASTOMA; GLIOMA; GLUCOSE METABOLISM; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOPRECIPITATION; LIQUID CHROMATOGRAPHY; MELANOMA; MITOSIS; MYELOFIBROSIS; NEOPLASM; NEUROBLASTOMA; PANCREAS CANCER; POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SEQUENCE ANALYSIS; SOLID TUMOR; THIN LAYER CHROMATOGRAPHY; THROMBOCYTHEMIA; ANALOGS AND DERIVATIVES; GENETICS; METABOLISM; NEOPLASMS;

5-METHYLCYTOSINE; CYTOSINE; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; DNA-BINDING PROTEINS; HUMANS; ISOCITRATE DEHYDROGENASE; NEOPLASMS; PROTO-ONCOGENE PROTEINS;

EID: 84930572740     PISSN: 22107762     EISSN: 22107770     Source Type: Journal    
DOI: 10.1016/j.cancergen.2015.02.009     Document Type: Review

References (160)

1. Hattori N., Ushijima T. Compendium of aberrant DNA methylation and histone modifications in cancer. Biochem Biophys Res Commun 2014, 455:3-9.
2. Neff T., Armstrong S.A. Recent progress toward epigenetic therapies: the example of mixed lineage leukemia. Blood 2013, 121:4847-4853.
3. Aumann S., Abdel-Wahab O. Somatic alterations and dysregulation of epigenetic modifiers in cancers. Biochem Biophys Res Commun 2014, 455:24-34.
4. Grossniklaus U., Paro R. Transcriptional silencing by polycomb-group proteins. Cold Spring Harb Perspect Biol 2014, 6:a019331.
5. Falkenberg K.J., Johnstone R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov 2014, 13:673-691.
6. Marsh D.J., Shah J.S., Cole A.J. Histones and their modifications in ovarian cancer - drivers of disease and therapeutic targets. Front Oncol 2014, 4:144.
7. McLean C.M., Karemaker I.D., van Leeuwen F. The emerging roles of DOT1L in leukemia and normal development. Leukemia 2014, 28:2131-2138.
8. Weber C.M., Henikoff S. Histone variants: dynamic punctuation in transcription. Genes & Development 2014, 28:672-682.
9. Abdel-Wahab O., Mullally A., Hedvat C., et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 2009, 114:144-147.
10. Ko M., Huang Y., Jankowska A.M., et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010, 468:839-843.
11. Pronier E., Almire C., Mokrani H., et al. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood 2011, 118:2551-2555.
12. Lian C.G., Xu Y., Ceol C., et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 2012, 150:1135-1146.
13. Orr B.A., Haffner M.C., Nelson W.G., et al. Decreased 5-hydroxymethylcytosine is associated with neural progenitor phenotype in normal brain and shorter survival in malignant glioma. PLoS ONE 2012, 7:e41036.
14. Bestor T., Laudano A., Mattaliano R., et al. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. JMol Biol 1988, 203:971-983.
15. Okano M., Xie S., Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 1998, 19:219-220.
16. Tahiliani M., Koh K.P., Shen Y., et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009, 324:930-935.
17. Ito S., Shen L., Dai Q., et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 2011, 333:1300-1303.
18. He Y.F., Li B.Z., Li Z., et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 2011, 333:1303-1307.
19. Kriaucionis S., Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 2009, 324:929-930.
20. Ghoshal A.K., Farber E. The induction of liver cancer by dietary deficiency of choline and methionine without added carcinogens. Carcinogenesis 1984, 5:1367-1370.
21. Jin S.-G., Kadam S., Pfeifer G.P. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res 2010, 38:e125.
22. Moran-Crusio K., Reavie L., Shih A., et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011, 20:11-24.
23. Vasanthakumar A., Lepore J.B., Zegarek M.H., et al. Dnmt3b is a haploinsufficient tumor suppressor gene in Myc-induced lymphomagenesis. Blood 2013, 121:2059-2063.
24. Madzo J., Liu H., Rodriguez A., et al. Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep 2014, 6:231-244.
25. Xu W., Yang H., Liu Y., et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011, 19:17-30.
26. Taiwo O., Wilson G.A., Morris T., et al. Methylome analysis using MeDIP-seq with low DNA concentrations. Nat Protoc 2012, 7:617-636.
27. Shen L., Wu H., Diep D., et al. Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics. Cell 2013, 153:692-706.
28. Mariani C.J., Madzo J., Moen E.L., et al. Alterations of 5-hydroxymethylcytosine in human cancers. Cancers (Basel) 2013, 5:786-814.
29. Pastor W.A., Pape U.J., Huang Y., et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 2011, 473:394-397.
30. Song C.-X., Szulwach K.E., Fu Y., et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 2011, 29:68-72.
31. Szulwach K.E., Li X., Li Y., et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci 2011, 14:1607-1616.
32. Mariani C.J., Vasanthakumar A., Madzo J., et al. TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Rep 2014, 7:1343-1352.
33. Yu M., Hon G.C., Szulwach K.E., et al. Tet-assisted bisulfite sequencing of 5-hydroxymethylcytosine. Nat Protoc 2012, 7:2159-2170.
34. Booth M.J., Ost T.W.B., Beraldi D., et al. Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine. Nat Protoc 2013, 8:1841-1851.
35. Booth M.J., Marsico G., Bachman M., et al. Quantitative sequencing of 5-formylcytosine in DNA at single-base resolution. Nat Chem 2014, 6:435-440.
36. Penn N.W., Suwalski R., O'Riley C., et al. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J 1972, 126:781-790.
37. Blattler A., Farnham P.J. Cross-talk between site-specific transcription factors and DNA methylation states. JBiol Chem 2013, 288:34287-34294.
38. Gu T.P., Guo F., Yang H., et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 2011, 477:606-610.
39. Iqbal K., Jin S.G., Pfeifer G.P., et al. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci U S A 2011, 108:3642-3647.
40. Wossidlo M., Nakamura T., Lepikhov K., et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun 2011, 2:241.
41. Ito S., D'Alessio A.C., Taranova O.V., et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010, 466:1129-1133.
42. Ficz G., Branco M.R., Seisenberger S., et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 2011, 473:398-402.
43. Lu F., Liu Y., Jiang L., et al. Role of Tet proteins in enhancer activity and telomere elongation. Genes Dev 2014, 28:2103-2119.
44. Wheldon L.M., Abakir A., Ferjentsik Z., et al. Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells. Cell Rep 2014, 7:1353-1361.
45. Koh K.P., Yabuuchi A., Rao S., et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 2011, 8:200-213.
46. Dawlaty M.M., Ganz K., Powell B.E., et al. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell 2011, 9:166-175.
47. Ko M., Bandukwala H.S., An J., et al. Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci U S A 2011, 108:14566-14571.
48. Li Z., Cai X., Cai C.-L., et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 2011, 118:4509-4518.
49. Quivoron C., Couronné L., Della Valle V., et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011, 20:25-38.
50. Shide K., Kameda T., Shimoda H., et al. TET2 is essential for survival and hematopoietic stem cell homeostasis. Leukemia 2012, 26:2216-2223.
51. Dawlaty M.M., Breiling A., Le T., et al. Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell 2014, 29:102-111.
52. Raiber E.-A., Murat P., Chirgadze D.Y., et al. 5-Formylcytosine alters the structure of the DNA double helix. Nat Struct Mol Biol 2015, 22:44-49.
53. Yildirim O., Li R., Hung J.-H., et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 2011, 147:1498-1510.
54. Spruijt C.G., Gnerlich F., Smits A.H., et al. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell 2013, 152:1146-1159.
55. Guilhamon P., Eskandarpour M., Halai D., et al. Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2. Nat Commun 2013, 4:2166.
56. Chen Q., Chen Y., Bian C., et al. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 2013, 493:561-564.
57. Deplus R., Delatte B., Schwinn M.K. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J 2013, 32:645-655.
58. Shi F.T., Kim H., Lu W., et al. Ten-eleven translocation 1 (Tet1) is regulated by O-linked N-acetylglucosamine transferase (Ogt) for target gene repression in mouse embryonic stem cells. JBiol Chem 2013, 288:20776-20784.
59. Vella P., Scelfo A., Jammula S., et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol Cell 2013, 49:645-656.
60. Ito R., Katsura S., Shimada H., et al. TET3-OGT interaction increases the stability and the presence of OGT in chromatin. Genes Cells 2014, 19:52-65.
61. Zhang Q., Liu X., Gao W., et al. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked β-N-acetylglucosamine transferase (OGT). JBiol Chem 2014, 289:5986-5996.
62. Slawson C., Lakshmanan T., Knapp S. Amitotic GlcNAcylation/phosphorylation signaling complex alters the posttranslational state of the cytoskeletal protein vimentin. Mol Biol Cell 2008, 19:4131-4140.
63. Fong J.J., Nguyen B.L., Bridger R., et al. β-N-Acetylglucosamine (O-GlcNAc) is a novel regulator of mitosis-specific phosphorylations on histone H3. JBiol Chem 2012, 287:12195-12203.
64. Figueroa M.E., Abdel-Wahab O., Lu C., et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010, 18:553-567.
65. Yamashita Y., Yuan J., Suetake I., et al. Array-based genomic resequencing of human leukemia. Oncogene 2010, 29:3723-3731.
66. Ley T.J., Ding L., Walter M.J., et al. DNMT3A mutations in acute myeloid leukemia. NEngl J Med 2010, 363:2424-2433.
67. Yan X.-J., Xu J., Gu Z.-H., et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011, 43:309-315.
68. Shen Y., Zhu Y.-M., Fan X., et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 2011, 118:5593-5603.
69. Abdel-Wahab O., Pardanani A., Rampal R., et al. DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia 2011, 25:1219-1220.
70. Stegelmann F., Bullinger L., Schlenk R.F., et al. DNMT3A mutations in myeloproliferative neoplasms. Leukemia 2011, 25:1217-1219.
71. Grossmann V., Haferlach C., Weissmann S., et al. The molecular profile of adult T-cell acute lymphoblastic leukemia: mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL. Genes Chromosomes Cancer 2013, 52:410-422.
72. Kim S.J., Zhao H., Hardikar S., et al. ADNMT3A mutation common in AML exhibits dominant-negative effects in murine ES cells. Blood 2013, 122:4086-4089.
73. Li K.K., Luo L.F., Shen Y., et al. DNA methyltransferases in hematologic malignancies. Semin Hematol 2013, 50:48-60.
74. Conway O'Brien E., Prideaux S., Chevassut T. The epigenetic landscape of acute myeloid leukemia. Adv Hematol 2014, 2014:103175.
75. Ono R., Taki T., Taketani T., et al. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res 2002, 62:4075-4080.
76. Lorsbach R.B., Moore J., Mathew S., et al. 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, 17:637-641.
77. Burmeister T., Meyer C., Schwartz S., et al. The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood 2009, 113:4011-4015.
78. Gelsi-Boyer V., Trouplin V., Adélaïde J., et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009, 145:788-800.
79. Kosmider O., Gelsi-Boyer V., Ciudad M., et al. TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica 2009, 94:1676-1681.
80. Langemeijer S.M.C., Aslanyan M.G., Jansen J.H. TET proteins in malignant hematopoiesis. Cell Cycle 2009, 8:4044-4048.
81. Langemeijer S., Kuiper R.P., Berends M., et al. Acquired mutations in tet2 are common in myelodysplastic syndromes. Nature Genet 2009, 41:838-842.
82. Mohamedali A.M., Smith A.E., Gaken J., et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. JClin Oncol 2009, 27:4002-4006.
83. Beer P.A., Delhommeau F., LeCouédic J.-P., et al. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood 2010, 115:2891-2900.
84. Colaizzo D., Tiscia G.L., Pisanelli D., et al. New TET2 gene mutations in patients with myeloproliferative neoplasms and splanchnic vein thrombosis. JThromb Haemost 2010, 8:1142-1144.
85. Couronné L., Lippert E., Andrieux J., et al. Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia 2010, 24:201-203.
86. Flach J., Dicker F., Schnittger S., et al. 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, 95:518-519.
87. Nibourel O., Kosmider O., Cheok M., et al. Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood 2010, 116:1132-1135.
88. Schaub F.X., Looser R., Li S., 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, 115:2003-2007.
89. Szpurka H., Jankowska A.M., Makishima H., et al. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations. Leuk Res 2010, 34:969-973.
90. Jankowska A.M., Szpurka H., Tiu R.V., et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009, 113:6403-6410.
91. Bacher U., Weissmann S., Kohlmann A., et al. TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele. Br J Haematol 2012, 156:67-75.
92. Yamazaki J., Taby R., Vasanthakumar A., et al. Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia. Epigenetics 2012, 7:201-207.
93. Abdel-Wahab O., Manshouri T., Patel J., et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res 2010, 70:447-452.
94. Corces-Zimmerman M.R., Hong W.-J., Weissman I.L., et al. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A 2014, 111:2548-2553.
95. Shlush L.I., Zandi S., Mitchell A., et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014, 506:328-333.
96. Gross S., Cairns R.A., Minden M.D. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. JExp Med 2010, 207:339-344.
97. Cazzola M. IDH1 and IDH2 mutations in myeloid neoplasms-novel paradigms and clinical implications. Haematologica 2010, 95:1623-1627.
98. Dang L., White D.W., Gross S., et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2010, 465:966.
99. Losman J.-A., Kaelin W.G. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 2013, 27:836-852.
100. Ward P.S., Patel J., Wise D.R., et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010, 17:225-234.
101. Koivunen P., Lee S., Duncan C.G., et al. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 2012, 483:484-488.
102. Tefferi A., Lasho T.L., Abdel-Wahab O., et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 2010, 24:1302-1309.
103. Marcucci G., Maharry K., Wu Y.-Z., et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. JClin Oncol 2010, 28:2348-2355.
104. Lin J., Yao D.-M., Qian J., et al. IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol 2012, 91:519-525.
105. Patnaik M.M., Hanson C.A., Hodnefield J.M., et al. Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic study of 277 patients. Leukemia 2012, 26:101-105.
106. Paschka P., Schlenk R.F., Gaidzik V.I., et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. JClin Oncol 2010, 28:3636-3643.
107. Chotirat S., Thongnoppakhun W., Promsuwicha O., et al. Molecular alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes and additional genetic mutations in newly diagnosed acute myeloid leukemia patients. JHematol Oncol 2012, 5:5.
108. Patel J.P., Gonen M., Figueroa M.E., et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. NEngl J Med 2012, 366:1079-1089.
109. Odejide O., Weigert O., Lane A.A., et al. Atargeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 2014, 123:1293-1296.
110. Jin S.-G., Jiang Y., Qiu R., et al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res 2011, 71:7360-7365.
111. Kudo Y., Tateishi K., Yamamoto K., et al. Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci 2012, 103:670-676.
112. Yang H., Liu Y., Bai F., et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene 2013, 32:663-669.
113. Jäwert F., Hasséus B., Kjeller G., et al. Loss of 5-hydroxymethylcytosine and TET2 in oral squamous cell carcinoma. Anticancer Res 2013, 33:4325-4328.
114. Hahn M.A., Qiu R., Wu X., et al. Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis. Cell Rep 2013, 3:291-300.
115. Jin S.-G., Wu X., Li A.X., et al. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res 2011, 39:5015-5024.
116. Nestor C.E., Ottaviano R., Reddington J., et al. Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes. Genome Res 2012, 22:467-477.
117. Amir R.E., Van den Veyver I.B., Wan M., et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999, 23:185-188.
118. Mellén M., Ayata P., Dewell S., et al. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 2012, 151:1417-1430.
119. Khare T., Pai S., Koncevicius K., et al. 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary. Nat Struct Mol Biol 2012, 19:1037-1043.
120. Parsons D.W., Jones S., Zhang X., et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
121. Yan H., Parsons D.W., Jin G., et al. IDH1 and IDH2 mutations in gliomas. NEngl J Med 2009, 360:765-773.
122. Dang L., Jin S., Su S.M. IDH mutations in glioma and acute myeloid leukemia. Trends Mol Med 2010, 16:387-397.
123. Noushmehr H., Weisenberger D.J., Diefes K., et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010, 17:510-522.
124. Turcan S., Rohle D., Goenka A., et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012, 483:479-483.
125. Althoff K., Beckers A., Bell E., et al. ACre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene 2014, [Epub ahead of print].
126. Gambichler T., Sand M., Skrygan M. Loss of 5-hydroxymethylcytosine and ten-eleven translocation 2 protein expression in malignant melanoma. Melanoma Res 2013, 23:218-220.
127. Larson A.R., Dresser K.A., Zhan Q., et al. Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors. Mod Pathol 2014, 27:936-944.
128. Lee J.J., Granter S.R., Laga A.C., et al. 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies. Mod Pathol 2015, 28:218-229.
129. Ghiam A.F., Cairns R.A., Thoms J., et al. IDH mutation status in prostate cancer. Oncogene 2012, 31:3826.
130. Bhattacharyya S., Yu Y., Suzuki M., et al. Genome-wide hydroxymethylation tested using the HELP-GT assay shows redistribution in cancer. Nucleic Acids Res 2013, 41:e157.
131. Amary M.F., Bacsi K., Maggiani F., et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. JPathol 2011, 224:334-343.
132. Arai M., Nobusawa S., Ikota H., et al. Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol 2012, 29:201-206.
133. Itzykson R., Kosmider O., Cluzeau T., et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 2011, 25:1147-1152.
134. Kroeze L.I., Aslanyan M.G., van Rooij A., et al. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. Blood 2014, 124:1110-1118.
135. Bejar R., Lord A., Stevenson K., et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014, 124:2705-2712.
136. Moen E.L., Stark A.L., Zhang W., et al. The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide. Mol Cancer Ther 2014, 13:1334-1344.
137. Yang X., Han H., De Carvalho D.D., et al. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell 2014, 26:511-590.
138. Chen J., Guo L., Zhang L., et al. Vitamin C modulates TET1 function during somatic cell reprogramming. Nat Genet 2013, 45:1504-1509.
139. Warburg O., Wind F., Negelein E. The metabolism of tumors in the body. JGen Physiol 1927, 8:519-530.
140. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
141. Losman J.-A., Looper R.E., Koivunen P., et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013, 339:1621-1625.
142. Delhommeau F., Dupont S., Della Valle V., et al. Mutation in TET2 in myeloid cancers. NEngl J Med 2009, 360:2289-2301.
143. Saint-Martin C., Leroy G., Delhommeau F., et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood 2009, 114:1628-1632.
144. Hussein K., Abdel-Wahab O., Lasho T.L., et al. Cytogenetic correlates of TET2 mutations in 199 patients with myeloproliferative neoplasms. Am J Hematol 2010, 85:81-83.
145. Tefferi A., Levine R.L., Lim K.-H., et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 2009, 23:900-904.
146. Tefferi A., Lim K.-H., Abdel-Wahab O., et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia 2009, 23:1343-1345.
147. Caramazza D., Lasho T.L., Finke C.M., et al. IDH mutations and trisomy 8 in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 2010, 24:2120-2122.
148. Pardanani A., Lasho T., Finke C., et al. LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 2010, 24:1713-1718.
149. Pardanani A., Patnaik M.M., Lasho T.L., et al. Recurrent IDH mutations in high-risk myelodysplastic syndrome or acute myeloid leukemia with isolated del(5q). Leukemia 2010, 24:1370-1372.
150. Tang J.Y., Chang C.C., Lin P.C., et al. Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and oral cancer. Kaohsiung J Med Sci 2012, 28:138-144.
151. Kang M.R., Kim M.S., Oh J.E., et al. Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 2009, 125:353-355.
152. Cairns R.A., Iqbal J., Lemonnier F., et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood 2012, 119:1901-1903.
153. Balss J., Meyer J., Mueller W., et al. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 2008, 116:597-602.
154. Hartmann C., Meyer J., Balss J., et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 2009, 118:469-474.
155. Nobusawa S., Watanabe T., Kleihues P., et al. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 2009, 15:6002-6007.
156. Pusch S., Sahm F., Meyer J., et al. Glioma IDH1 mutation patterns off the beaten track. Neuropathol Appl Neurobiol 2011, 37:428-430.
157. Pansuriya T.C., van Eijk R., d'Adamo P., et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 2011, 43:1256-1261.
158. Borger D.R., Tanabe K.K., Fan K.C., et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012, 17:72-79.
159. Gaal J., Burnichon N., Korpershoek E., et al. Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas. JClin Endocrinol Metab 2010, 95:1274-1278.
160. Murugan A.K., Bojdani E., Xing M. Identification and functional characterization of isocitrate dehydrogenase 1 (IDH1) mutations in thyroid cancer. Biochem Biophys Res Commun 2010, 393:555-559.