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TET2 Mutations Affect Non-CpG Island DNA Methylation at Enhancers and Transcription Factor–Binding Sites in Chronic Myelomonocytic Leukemia

Yamazaki, Jumpei, Jelinek, Jaroslav, Lu, Yue, Cesaroni, Matteo, Madzo, Jozef, Neumann, Frank, He, Rong, Taby, Rodolphe, Vasanthakumar, Aparna, Macrae, Trisha, Ostler, Kelly R., Kantarjian, Hagop M., Liang, Shoudan, Estecio, Marcos R., Godley, Lucy A., Issa, Jean-Pierre J.·2015·Cancer Research
DOI 10.1158/0008-5472.can-14-0739PMC PMC4506197

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Abstract

TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well as other covalently modified cytosines and its mutations are common in myeloid leukemia. However, the exact mechanism and the extent to which TET2 mutations affect DNA methylation remain in question. Here, we report on DNA methylomes in TET2 wild-type (TET2-WT) and mutant (TET2-MT) cases of chronic myelomonocytic leukemia (CMML). We analyzed 85,134 CpG sites [28,114 sites in CpG islands (CGI) and 57,020 in non-CpG islands (NCGI)]. TET2 mutations do not explain genome-wide differences in DNA methylation in CMML, and we found few and inconsistent differences at CGIs between TET2-WT and TET2-MT cases. In contrast, we identified 409 (0.71%) TET2-specific differentially methylated CpGs (tet2-DMCs) in NCGIs, 86% of which were hypermethylated in TET2-MT cases, suggesting a strikingly different biology of the effects of TET2 mutations at CGIs and NCGIs. DNA methylation of tet2-DMCs at promoters and nonpromoters repressed gene expression. Tet2-DMCs showed significant enrichment at hematopoietic-specific enhancers marked by H3K4me1 and at binding sites for the transcription factor p300. Tet2-DMCs showed significantly lower 5-hydroxymethylcytosine in TET2-MT cases. We conclude that leukemia-associated TET2 mutations affect DNA methylation at NCGI regions containing hematopoietic-specific enhancers and transcription factor–binding sites. Cancer Res; 75(14); 2833–43. ©2015 AACR.

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Citations

Cites

Research works printed but not linked: 36

  1. Tefferi, 2009, Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates, Leukemia, 23, 900, 10.1038/leu.2009.37 · DOI
  2. Tefferi, 2009, Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML, Leukemia, 23, 1343, 10.1038/leu.2009.59 · DOI
  3. Langemeijer, 2009, Acquired mutations in TET2 are common in myelodysplastic syndromes, Nat Genet, 41, 838, 10.1038/ng.391 · DOI · Paper page
  4. Jankowska, 2009, Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms, Blood, 113, 6403, 10.1182/blood-2009-02-205690 · DOI · Paper page
  5. Abdel-Wahab, 2009, Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies, Blood, 114, 144, 10.1182/blood-2009-03-210039 · DOI · Paper page
  6. Kosmider, 2009, TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia, Haematologica, 94, 1676, 10.3324/haematol.2009.011205 · DOI
  7. Tahiliani, 2009, Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1, Science, 324, 930, 10.1126/science.1170116 · DOI · Paper page
  8. Ito, 2010, Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification, Nature, 466, 1129, 10.1038/nature09303 · DOI · Paper page
  9. He, 2011, Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA, Science, 333, 1303, 10.1126/science.1210944 · DOI
  10. Ko, 2010, Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2, Nature, 468, 839, 10.1038/nature09586 · DOI · Paper page
  11. Quivoron, 2011, TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis, Cancer Cell, 20, 25, 10.1016/j.ccr.2011.06.003 · DOI · Paper page
  12. Yamazaki, 2012, Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia, Epigenetics, 7, 201, 10.4161/epi.7.2.19015 · DOI
  13. Perez, 2012, TET2 mutations are associated with specific 5-methylcytosine and 5-hydroxymethylcytosine profiles in patients with chronic myelomonocytic leukemia, PLoS One, 7, e31605, 10.1371/journal.pone.0031605 · DOI
  14. Challen, 2012, Dnmt3a is essential for hematopoietic stem cell differentiation, Nat Genet, 44, 23, 10.1038/ng.1009 · DOI · Paper page
  15. Kantarjian, 2006, Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study, Cancer, 106, 1794, 10.1002/cncr.21792 · DOI
  16. Ng, 2006, Predicting the effects of amino acid substitutions on protein function, Annu Rev Genomics Hum Genet, 7, 61, 10.1146/annurev.genom.7.080505.115630 · DOI
  17. Kosmider, 2010, Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms, Leukemia, 24, 1094, 10.1038/leu.2010.52 · DOI
  18. Walter, 2011, Recurrent DNMT3A mutations in patients with myelodysplastic syndromes, Leukemia, 25, 1153, 10.1038/leu.2011.44 · DOI · Paper page
  19. Jelinek, 2012, Conserved DNA methylation patterns in healthy blood cells and extensive changes in leukemia measured by a new quantitative technique, Epigenetics, 7, 1368, 10.4161/epi.22552 · DOI
  20. Gardiner-Garden, 1987, CpG islands in vertebrate genomes, J Mol Biol, 196, 261, 10.1016/0022-2836(87)90689-9 · DOI
  21. Colella, 2003, Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites, Biotechniques, 35, 146, 10.2144/03351md01 · DOI
  22. Braun, 2011, Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial, Blood, 118, 3824, 10.1182/blood-2011-05-352039 · DOI
  23. Consortium, 2012, An integrated encyclopedia of DNA elements in the human genome, Nature, 489, 57, 10.1038/nature11247 · DOI · Paper page
  24. Flicek, 2014, Ensembl 2014, Nucleic Acids Res, 42, D749, 10.1093/nar/gkt1196 · DOI
  25. Song, 2011, Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine, Nat Biotechnol, 29, 68, 10.1038/nbt.1732 · DOI
  26. Wu, 2011, Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells, Nature, 473, 389, 10.1038/nature09934 · DOI · Paper page
  27. Williams, 2012, DNA methylation: TET proteins-guardians of CpG islands?, EMBO Rep, 13, 28, 10.1038/embor.2011.233 · DOI
  28. Vo, 2001, CREB-binding protein and p300 in transcriptional regulation, J Biol Chem, 276, 13505, 10.1074/jbc.R000025200 · DOI
  29. Yu, 2012, Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome, Cell, 149, 1368, 10.1016/j.cell.2012.04.027 · DOI
  30. Ficz, 2011, Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation, Nature, 473, 398, 10.1038/nature10008 · DOI
  31. Stroud, 2011, 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells, Genome Biol, 12, R54, 10.1186/gb-2011-12-6-r54 · DOI
  32. Hon, 2014, 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation, Mol Cell, 56, 286, 10.1016/j.molcel.2014.08.026 · DOI · Paper page
  33. Lu, 2014, Role of Tet proteins in enhancer activity and telomere elongation, Genes Dev, 28, 2103, 10.1101/gad.248005.114 · DOI
  34. Asmar, 2013, Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma, Haematologica, 98, 1912, 10.3324/haematol.2013.088740 · DOI
  35. Busque, 2012, Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis, Nat Genet, 44, 1179, 10.1038/ng.2413 · DOI · Paper page
  36. Shen, 2010, DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes, J Clin Oncol, 28, 605, 10.1200/JCO.2009.23.4781 · DOI

Cited by

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Metadata

Authors
Yamazaki, J., Jelinek, J., Lu, Y., Cesaroni, M., Madzo, J., Neumann, F., He, R., Taby, R., Vasanthakumar, A., Macrae, T., Ostler, K. R., Kantarjian, H. M., Liang, S., Estecio, M. R., Godley, L. A., & Issa, J.-P. J.
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2015-07-14
Volume
75
Issue
14
Pages
2833-2843
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-14-0739
PMC
PMC4506197
Cited by
89
References
10
Language
en

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