The epigenetics of cancer in children

Klinische Padiatrie

Volumn 220, Issue 6, 2008, Pages 333-341

  Frühwald, Michael C ^a   Witt, Olaf ^b,c  

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

DNMT; Epigenetics; HDAC; Inhibitors; Pediatric oncology

Indexed keywords

4 AMINOBENZOIC ACID DERIVATIVE; 4 N ACETYLDINALINE; 5 AZA 2' DEOXYCYTIDINE; ANTISENSE OLIGONUCLEOTIDE; AZACITIDINE; CARBOPLATIN; DNA METHYLTRANSFERASE INHIBITOR; ETOPOSIDE; HC TOXIN; HISTONE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; MELPHALAN; MG 98; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; NUCLEOSIDE ANALOG; PROCAINAMIDE; PROCAINE; RETINOIC ACID; RG 108; ROMIDEPSIN; TETRAPEPTIDE; TRICHOSTATIN A; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VINCRISTINE; VORINOSTAT; ZEBULARINE;

ANTINEOPLASTIC ACTIVITY; BONE MARROW TOXICITY; CANCER GROWTH; CANCER RESISTANCE; CARCINOGENESIS; CARDIOTOXICITY; CHILD; CHILD HEALTH CARE; CHILDHOOD CANCER; CLINICAL TRIAL; DNA METHYLATION; DNA SEQUENCE; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; ELECTROCARDIOGRAM; ENZYME ACTIVITY; EPIGENETICS; EXCITATION; FATIGUE; GASTROINTESTINAL SYMPTOM; HIGH RISK POPULATION; HUMAN; LIVER TOXICITY; MALIGNANT TRANSFORMATION; MOLECULAR BIOLOGY; MULTIMODALITY CANCER THERAPY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN MODIFICATION; REVIEW; SIDE EFFECT; SOLID TUMOR; THROMBOCYTOPENIA; TRANSCRIPTION REGULATION; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; CHILD; CYTIDINE; DISEASE PROGRESSION; DNA MODIFICATION METHYLASES; DRUG RESISTANCE, NEOPLASM; DRUGS, INVESTIGATIONAL; EPIGENESIS, GENETIC; HISTONE DEACETYLASES; HUMANS; NEOPLASMS; TRANSCRIPTION, GENETIC;

EID: 56349154920     PISSN: 03008630     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0028-1086026     Document Type: Review

References (133)

1. Antequera F, Bird A. Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci USA 1993; 90: 11995-11999
2. Aparicio A, Eads CA, Leong LA et al. Phase I trial of continuous infusion 5-aza-2′-deoxycytidine. Cancer Chemother Pharmacol 2003; 51: 231-239
3. Balch C, Montgomery JS, Paik HI et al. New anti-cancer strategies: epigenetic therapies and biomarkers. Front Biosci 2005; 10: 1897-1931
4. Bali P, Pranpat M, Bradner J et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 2005; 280: 26729-26734
5. Bayani J, Selvarajah S, Maire G et al. Genomic mechanisms and measurement of structural and numerical instability in cancer cells. Semin Cancer Biol 2007; 17: 5-18
6. Bhalla KN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol 2005; 23: 3971-3993
7. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16: 6-21
8. Bjornsson HT, Brown LJ, Fallin MD et al. Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. J Natl Cancer Inst 2007; 99: 1270-1273 Epub 2007 Aug 1278
9. Blumenschein G, Lu G, Kies M et al. Phase II clinical trial of suberoylanilide hydroxamic acid (SAHA) in patients with recurrent and/or metastatic head and neck cancer(SCCHN). Invest New Drugs 2008; 26: 81-87
10. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5: 769-784
11. Brueckner B, Boy RG, Siedlecki P et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 2005; 65: 6305-6311
12. Byrd JC, Marcucci G, Parthun MR et al. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 2005; 105: 959-967
13. Cameron EE, Bachman KE, Myohanen S et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999; 21: 103-107
14. Chavez-Blanco A, Segura-Pacheco B, Perez-Cardenas E et al. Histone acetylation and histone deacetylase activity of magnesium valproate in tumor and peripheral blood of patients with cervical cancer. A phase I study. Mol Cancer 2005; 4: 22
15. Cheng JC, Matsen CB, Gonzales FA et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst 2003; 95: 399-409
16. Cheng JC, Yao CB, Weisenberger DJ et al. Preferential response of cancer cells to zebularine. Cancer Cell 2004; 6: 151-158
17. Cinatl J Jr, Cinatl J, Scholz M et al. Antitumor activity of sodium valproate in cultures of human neuroblastoma cells. Anticancer Drugs 1996; 7: 766-773
18. Cooper DN, Krawczak M. Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes. Hum Genet 1989; 83: 181-188
19. Costello JF, Fruhwald MC, Smiraglia DJ et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 2000; 24: 132-138
20. Davis AJ, Gelmon KA, Siu LL et al. Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks. Invest New Drugs 2003; 21: 85-97
21. Deubzer HE, Ehemann V, Kulozik AE et al. Anti-neuroblastoma activity of Helminthosporium carbonum (HC)-toxin is superior to that of other differentiating compounds in vitro. Cancer Lett 2008; 264: 21-28
22. Deubzer HE, Ehemann V, Westermann F et al. Inhibiting histone deacetylases in neuroblastoma. Klin Padiatr 2007; 219: 183
23. Deubzer HE, Ehemann V, Westermann F et al. Histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the malignant phenotype of neuroblastoma cells. Int J Cancer 2008; 122: 1891-1900
24. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007; 5: 981-989
25. Donson AM, Addo-Yobo SO, Handler MH et al. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer 2007; 48: 403-407
26. Ebinger M, Senf L, Scheurlen W. Risk stratification in medulloblastoma: screening for molecular markers. Klin Padiatr 2006; 218: 139-142
27. Eden A, Gaudet F, Waghmare A et al. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 2003; 300: 455
28. Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene 2002; 21: 5400-5413
29. Einsiedel HG, Kawan L, Eckert C et al. Histone deacetylase inhibitors have antitumor activity in two NOD/SCID mouse models of B-cell precursor childhood acute lymphoblastic leukemia. Leukemia 2006; 20: 1435-1436
30. Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358: 1148-1159
31. Esteller M. Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 2005; 45: 629-656
32. Feinberg AP. Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res 1999; 59: 1743s-1746s
33. Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature 2007; 447: 433-440
34. Feinberg AP. Epigenetics at the epicenter of modern medicine. Jama 2008; 299: 1345-1350
35. Fouladi M, Furman WL, Chin T et al. Phase I study of depsipeptide in pediatric patients with refractory solid tumors: a Children's Oncology Group report. J Clin Oncol 2006; 24: 3678-3685
36. Fraga MF, Ballestar E, Villar-Garea A et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 2005; 37: 391-400
37. Frühwald MC. DNA methylation patterns in cancer: novel prognostic indicators? Am J Pharmacogenomics 2003; 3: 245-260
38. Frühwald MC, O'Dorisio MS, Dai Z et al. Aberrant promoter methylation of previously unidentified target genes is a common abnormality in medulloblastomas- Implications for tumor biology and potential clinical utility. Oncogene 2001; 20: 5033-5042
39. Frühwald MC, O'Dorisio MS, Dai Z et al. Aberrant hypermethylation of the major breakpoint cluster region in 17p11.2 in medulloblastomas but not supratentorial PNETs. Genes, Chromosomes & Cancer 2001; 30: 38-47
40. Frühwald MC, O'Dorisio MS, Smith L et al. Hypermethylation as a potential prognostic factor and a clue to a better understanding of the molecular pathogenesis of medulloblastoma - results of a genome-wide methylation scan. Klin Padiatr 2001; 213: 197-203
41. Frühwald MC, Plass C. Global and gene-specific methylation patterns in cancer: aspects of tumor biology and clinical potential. Mol Genet Metab 2002; 75: 1-16
42. Fujita N, Watanabe S, Ichimura T et al. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem 2003; 278: 24132-24138
43. Fukuzawa R, Anaka M, Heathcott R et al. Wilms tumour histology is determined by distinct types of precursor lesions and not epigenetic changes. J Pathol 2008; 215: 377-387
44. Fukuzawa R, Reeve AE. Molecular pathology and epidemiology of nephrogenic rests and Wilms tumors. J Pediatr Hematol Oncol 2007; 29: 589-594
45. Furchert SE, Lanvers-Kaminsky C, Jurgens H et al. Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood. Int J Cancer 2007; 120: 1787-1794
46. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B et al. Phase 1/ 2 study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 2006; 108: 3271-3279
47. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol 1987; 196: 261-282
48. Gaudet F, Hodgson JG, Eden A et al. Induction of tumors in mice by genomic hypomethylation. Science 2003; 300: 489-492
49. Glaser KB, Li J, Staver MJ et al. Role of class I and class II histone deacetylases in carcinoma cells using siRNA. Biochem Biophys Res Commun 2003; 310: 529-536
50. Gore SD, Baylin S, Sugar E et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66: 6361-6369
51. Gottlicher M, Minucci S, Zhu P et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. Embo J 2001; 20: 6969-6978
52. Graham C, Tucker C, Creech J et al. Evaluation of the antitumor efficacy, pharmacokinetics, and pharmacodynamics of the histone deacetylase inhibitor depsipeptide in childhood cancer models in vivo. Clin Cancer Res 2006; 12: 223-234
53. Grant S, Easley C, Kirkpatrick P. Vorinostat. Nat Rev Drug Discov 2007; 6: 21-22
54. Haggarty SJ, Koeller KM, Wong JC et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003; 100: 4389-4394
55. Hahnen E, Eyupoglu IY, Brichta L et al. In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. J Neurochem 2006; 98: 193-202
56. Harms D, Zahn S, Göbel U et al. Pathology and molecular biology of teratomas in childhood and adolescence. Klin Padiatr 2006; 218: 296-302
57. Hegi ME, Diserens AC, Gorlia T et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352: 997-1003
58. Hitchins MP, Wong JJ, Suthers G et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med 2007; 356: 697-705
59. Hockly E, Richon VM, Woodman B et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci USA 2003; 100: 2041-2046
60. Holleran JL, Parise RA, Joseph E et al. Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyltransferase inhibitor, zebularine. Clin Cancer Res 2005; 11: 3862-3868
61. Issa JP, Garcia-Manero G, Giles FJ et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103: 1635-1640
62. Issa JP, Ottaviano YL, Celano P et al. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 1994; 7: 536-540
63. Jaboin J, Wild J, Hamidi H et al. M5-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors. Cancer Res 2002; 62: 6108-6115
64. Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol 2007; 211: 261-268
65. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128: 683-692
66. Kantarjian HM, O'Brien S, Cortes J et al. Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer 2003; 98: 522-528
67. Kantarjian H, Oki Y, Garcia-Manero G et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007; 109: 52-57
68. Kelly WK, O'Connor O A, Krug LM et al. Phase I Study of an Oral Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid, in Patients With Advanced Cancer. J Clin Oncol 2005; 16: 16
69. Kelly WK, Richon VM, O'Connor O et al. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin Cancer Res 2003; 9: 3578-3588
70. Keshelava N, Davicioni E, Wan Z et al. Histone deacetylase I gene expression and sensitization of multidrug-resistant neuroblastoma cell lines to cytotoxic agents by depsipeptide. J Natl Cancer Inst 2007; 99: 1107-1119
71. Khan N, Jeffers M, Kumar S et al. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J 2008; 409: 581-589
72. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer 2001; 1: 157-162
73. Kopelovich L, Crowell JA, Fay JR. The epigenome as a target for cancer chemoprevention. J Natl Cancer Inst 2003; 95: 1747-1757
74. Kornblith AB, Herndon 2nd JE, Silverman LR et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol 2002; 20: 2441-2452
75. Kraker AJ, Mizzen CA, Hartl BG et al. Modulation of histone acetylation by [4-(acetylamino)-N-(2-amino-phenyl) benzamide] in HCT-8 colon carcinoma. Mol Cancer Ther 2003; 2: 401-408
76. Kramer OH, Zhu P, Ostendorff HP et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. Embo J 2003; 22: 3411-3420
77. Laird PW. Cancer epigenetics. Hum Mol Genet 2005; 14 (Spec No 1): R65-R76
78. Li Y, Zhang X, Polakiewicz RD et al. HDAC6 is required for EGF-induced beta -catenin nuclear localization. J Biol Chem 2008; 283: 12686-12690
79. Lin X, Asgari K, Putzi MJ et al. Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. Cancer Res 2001; 61: 8611-8616
80. Lindsey JC, Lusher ME, Anderton JA et al. Identification of tumour-specific epigenetic events in medulloblastoma development by hypermethylation profiling. Carcinogenesis 2004; 25: 661-668
81. Lujambio A, Ropero S, Ballestar E et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 2007; 67: 1424-1429
82. Lusher ME, Lindsey JC, Latif F et al. Biallelic epigenetic inactivation of the RASSF1A tumor suppressor gene in medulloblastoma development. Cancer Res 2002; 62: 5906-5911
83. Lyko F, Brown R. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst 2005; 97: 1498-1506
84. Mack GS. Epigenetic cancer therapy makes headway. J Natl Cancer Inst 2006; 98: 1443-1444
85. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006; 6: 38-51
86. Momparler RL, Rivard GE, Gyger M. Clinical trial on 5-aza-2′-deoxycytidine in patients with acute leukemia. Pharmacol Ther 1985; 30: 277-286
87. Momparler RL, Cote S, Eliopoulos N. Pharmacological approach for optimization of the dose schedule of 5-Aza-2′-deoxycytidine (Decitabine) for the therapy of leukemia. Leukemia 1997; 11 (Suppl 1): S1-S6
88. Mottet D, Bellahcene A, Pirotte S et al. Histone deacetylase 7 silencing alters endothelial cell migration, a key step in angiogenesis. Circ Res 2007; 101: 1237-1246
89. Mühlisch J, Bajanowski T, Rickert CH et al. Frequent but borderline methylation of p16 (INK4a) and TIMP3 in medulloblastoma and sPNET revealed by quantitative analyses. J Neurooncol 2007; 83: 17-29
90. Mühlisch J, Schwering A, Grotzer M et al. Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood. Oncogene 2006; 25: 1111-1117
91. Murrell A, Rakyan VK, Beck S. From genome to epigenome. Hum Mol Genet 2005; 14 (Spec No 1): R3-R10
92. Oberndorfer S, Piribauer M, Marosi C et al. P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J Neurooncol 2005; 72: 255-260
93. Oehme I, Deubzer HE, Wegener D et al. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res in press 2008
94. Parham DM, Ellison DA. Rhabdomyosarcomas in adults and children: ah update. Arch Pathol Lab Med 2006; 130: 1454-1465
95. Park JH, Kim SH, Choi MC et al. Class 11 histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors. Biochem Biophys Res Commun 2008; 368: 318-322
96. Pauer LR, Olivares J, Cunningham C et al. Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors. Cancer Invest 2004; 22: 886-896
97. Pfeifer GP, You YH, Besaratinia A. Mutations induced by ultraviolet light. Mutat Res 2005; 571: 19-31
98. Piekarz RL, Robey R, Sandor V et al. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood 2001; 98: 2865-2868
99. Pohlmann P, DiLeone LP, Cancella AI et al. Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. Am J Clin Oncol 2002; 25: 496-501
100. Prakash S, Foster BJ, Meyer M et al. Chronic oral administration of CI-994: a phase 1 study. Invest New Drugs 2001; 19: 1-11
101. Qian DZ, Kachhap SK, Collis SJ et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res 2006; 66: 8814-8821
102. Rollins RA, Haghighi F, Edwards JR et al. Large-scale structure of genomic methylation patterns. Genome Res 2006; 16: 157-163
103. Ryan QC, Headlee D, Acharya M et al. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 2005; 23: 3912-3922
104. Saito A, Yamashita T, Mariko Y et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 1999; 96: 4592-4597
105. Sandor V, Bakke S, Robey RW et al. Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. Clin Cancer Res 2002; 8: 718-728
106. Schlosser S, Frühwald MC. Epigenetic mechanisms in the development of malignancies of the central nervous system (CNS). In, Trends in Brain Cancer Research. San Francisco: Novaeditorial Publishers; 2008, in press
107. Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E et al. Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res 2003; 9: 1596-1603
108. Shan B, Yao TP, Nguyen HT et al. Requirement of HDAC6 for TGF-beta 1-induced epithelial-mesenchymal transition. J Biol Chem 2008; 283: 21065-21073
109. Singal R, Ginder GD. DNA methylation. Blood 1999; 93: 4059-4070
110. Sonnemann J, Kumar KS, Heesch S et al. Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. Int J Oncol 2006; 28: 755-766
111. Soriano AO, Yang H, Faderl S et al. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 2007; 110: 2302-2308
112. Sparago A, Russo S, Cerrato F et al. Mechanisms causing imprinting defects in familial Beckwith-Wiedemann syndrome with Wilms' tumour. Hum Mol Genet 2007; 16: 254-264 Epub 2006 Dec 2011
113. Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet 2004; 36: 497-501 Epub 2004 Apr 2004
114. Tabe Y, Jin L, Contractor R et al. Novel role of HDAC inhibitors in AML1/ETO AML cells: activation of apoptosis and phagocytosis through induction of annexin A1. Cell Death Differ 2007; 14: 1443-1456
115. Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 2002; 99: 3740-3745
116. Ting AH, MacGarvey KM, Baylin SB. The cancer epigenome-components and functional correlates. Genes Dev 2006; 20: 3215-3231
117. Turker MS, Bestor TH. Formation of methylation patterns in the mammalian genome. Mutat Res 1997; 386: 119-130
118. Ushijima T, Okochi-Takada E. Aberrant methylations in cancer cells: where do they come from? Cancer Sci 2005: 96: 206-211
119. Vanhaecke T, Papeleu P, Elaut G et al. Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view. Curr Med Chem 2004; 11: 1629-1643
120. Villar-Garea A, Fraga MF, Espada J et al. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res 2003; 63: 4984-4989
121. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia http://wwwclinicaltrialsgov/ct/show/NCT00217412?order=1 Children's Oncology Group (NCT00217412)
122. Waddington CH. The Epigenotype. Endeavour 1942; 1: 18-2053.
123. Weichert W, Roske A, Gekeler V et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol 2008;9:139-148.
124. Watt PM, Kumar R, Kees UR. Promoter demethylation accompanies reactivation of the HOX11 proto-oncogene in leukemia. Genes Chromosomes Cancer 2000; 29: 371-377
125. Wegener D, Deubzer HE, Oehme I et al. A novel HDAC inhibitor identified in the screening of a compound library id effective in neuroblastoma cells. Klin Padiatr 2007; 219: 195
126. Weichert W, Roske A, Gekeler V et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol 2008; 9: 139-148
127. Weichert W, Roske A, Niesporek S et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res 2008; 14: 1669-1677
128. Witt O, Deubzer H, Milde T et al. HDAC family: what are the cancer relevant targets? Cancer Lett in press 2008
129. Witt O, Kanbach K, Krenz K et al. Induction of tumor cell differentiation by histone-deacetylase inhibitors. Klin Padiatr 2002; 214: 257
130. Witt O, Monkemeyer S, Ronndahl G et al. Induction of fetal hemoglobin expression by the histone deacetylase inhibitor apicidin. Blood 2003; 101: 2001-2007
131. Witt O, Sand K, Pekrun A. Butyrate-induced erythroid differentiation of human K562 leukemia cells involves inhibition of ERK and activation of p38 MAP kinase pathways. Blood 2000; 95: 2391-2396
132. Witt O, Schweigerer L, Driever PH et al. Valproic acid treatment of glioblastoma multiforme in a child. Pediatr Blood Cancer 2004; 43: 181
133. Yoon JH, Smith LE, Feng Z et al. Methylated CpG dinucleotides are the preferential targets for G-to-T transversion mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities with the p53 mutation spectrum in smoking-associated lung cancers. Cancer Res 2001; 61: 7110-7117