Cancer epigenetics

CA Cancer Journal for Clinicians

Volumn 60, Issue 6, 2010, Pages 376-392

  Taby, Rodolphe ^a   Issa, Jean Pierre ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; DEPSIPEPTIDE; DNA; DNA METHYLTRANSFERASE INHIBITOR; HISTONE; HISTONE DEACETYLASE INHIBITOR; MICRORNA; PROCAINAMIDE; SGI 1027; TEMOZOLOMIDE; TUMOR MARKER; UNCLASSIFIED DRUG; UNTRANSLATED RNA; VORINOSTAT; ZEBULARINE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW SUPPRESSION; CANCER CLASSIFICATION; CANCER DIAGNOSIS; CANCER GROWTH; CANCER INVASION; CANCER PREVENTION; CANCER RISK; CANCER SURVIVAL; CARCINOGENESIS; CLINICAL TRIAL; CUTANEOUS T CELL LYMPHOMA; DNA METHYLATION; DRUG TARGETING; EPIGENETICS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC CODE; GLIOBLASTOMA; HUMAN; LUNG NON SMALL CELL CANCER; LUNG SURGERY; MALIGNANT NEOPLASTIC DISEASE; MYELODYSPLASTIC SYNDROME; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; PROTEIN MODIFICATION; PROTEIN PROCESSING; RISK ASSESSMENT; SIGNAL TRANSDUCTION; SOLID TUMOR; TREATMENT RESPONSE; TUMOR BIOPSY;

ANIMALS; CELL CYCLE; CELL TRANSFORMATION, NEOPLASTIC; DNA METHYLATION; EPIGENESIS, GENETIC; HISTONES; HUMANS; MICRORNAS; NEOPLASM INVASIVENESS; NEOPLASMS; PROGNOSIS; RISK ASSESSMENT; TUMOR MARKERS, BIOLOGICAL;

EID: 78649383152     PISSN: 00079235     EISSN: 15424863     Source Type: Journal    
DOI: 10.3322/caac.20085     Document Type: Article

References (160)

1. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089-1093.
2. Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23:314-318.
3. Wang Y, Jorda M, Jones PL, et al. Functional CpG methylation system in a social insect. Science. 2006;314:645-647.
4. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89-97.
5. Glass JL, Thompson RF, Khulan B, et al. CG dinucleotide clustering is a speciesspecific property of the genome. Nucleic Acids Res. 2007;35:6798-6807.
6. Illingworth RS, Bird AP. CpG islands-'a rough guide.' FEBS Lett. 2009;583:1713- 1720.
7. Nan X, Ng HH, Johnson CA, et al. Transcriptional repression by the methyl-CpGbinding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393: 386-389.
8. Zoghbi HY. Rett syndrome: what do we know for sure? Nat Neurosci. 2009;12: 239-240.
9. Bestor TH, Tycko B. Creation of genomic methylation patterns. Nat Genet. 1996;12: 363-367.
10. Mohandas T, Sparkes RS, Shapiro LJ. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science. 1981;211: 393-396.
11. Swain JL, Stewart TA, Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell. 1987;50:719-727.
12. Shen L, Kondo Y, Guo Y, et al. Genomewide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 2007;3: 2023-2036.
13. Wilson VL, Jones PA. DNA methylation decreases in aging but not in immortal cells. Science. 1983;220:1055-1057.
14. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994;7:536-540.
15. Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging andDNAmethylation in colorectal mucosa and cancer. Cancer Res. 1998; 58:5489-5494.
16. Maegawa S, Hinkal G, Kim HS, et al. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 2010;20:332-340.
17. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102:10604-10609.
18. Jones PA, Liang G. Rethinking how DNA methylation patterns are maintained. Nat Rev Genet. 2009;10:805-811.
19. Jair KW, Bachman KE, Suzuki H, et al. De novo CpG island methylation in human cancer cells. Cancer Res. 2006;66:682-692.
20. Bestor TH, Verdine GL. DNA methyltransferases. Curr Opin Cell Biol. 1994; 6: 380-389.
21. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992;69:915-926.
22. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41-45.
23. Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 1998;12:599-606.
24. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009;78:273-304.
25. Yang XJ. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res. 2004;32:959-976.
26. Utley RT, Ikeda K, Grant PA, et al. Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature. 1998;394:498-502.
27. Yang XJ, Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene. 2007;26:5310-5318.
28. Ashburner BP, Westerheide SD, Baldwin AS Jr. The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol Cell Biol. 2001;21:7065-7077.
29. Tell G, Quadrifoglio F, Tiribelli C, Kelley MR. The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal. 2009;11:601-620.
30. Ikenoue T, Inoki K, Zhao B, Guan KL. PTEN acetylation modulates its interaction with PDZ domain. Cancer Res. 2008; 68:6908-6912.
31. Vaziri H, Dessain SK, Ng Eaton E. et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001; 107: 149-159.
32. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074-1080.
33. Lachner M, Jenuwein T. The many faces of histone lysine methylation. Curr Opin Cell Biol. 2002;14:286-298.
34. Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004; 119:941-953.
35. Tsukada Y, Fang J, Erdjument-Bromage H, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811-816.
36. Zhang K, Lin W, Latham JA, et al. The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation. Cell. 2005;122:723-734.
37. Segal E, Fondufe-Mittendorf Y, Chen L, et al. A genomic code for nucleosome positioning. Nature. 2006;442:772-778.
38. Schones DE, Cui K, Cuddapah S, et al. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008; 132:887-898.
39. Weissman B, Knudsen KE. Hijacking the chromatin remodeling machinery: impact of SWI/SNF perturbations in cancer. Cancer Res. 2009;69:8223-8230.
40. Langst G, Becker PB. Nucleosome remodeling: one mechanism, many phenomena? Biochim Biophys Acta. 2004;1677:58-63.
41. Ghildiyal M, Zamore PD. Small silencing RNAs: an expanding universe. Nat Rev Genet. 2009;10:94-108.
42. Davalos V, Esteller M. MicroRNAs and cancer epigenetics: a macrorevolution. Curr Opin Oncol. 2010;22:35-45.
43. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769-773.
44. Schickel R, Boyerinas B, Park SM, Peter ME. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 2008;27: 5959-5974.
45. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789-799.
46. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128:683-692.
47. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. NEngl J Med. 2003; 349: 2042-2054.
48. Myohanen SK, Baylin SB, Herman JG. Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. Cancer Res. 1998;58:591-593.
49. Zardo G, Tiirikainen MI, Hong C, et al. Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors. Nat Genet. 2002;32:453-458.
50. Schuebel KE, Chen W, Cope L, et al. Comparing theDNAhypermethylome with gene mutations in human colorectal cancer. PLoS Genet. 2007;3:1709-1723.
51. Suzuki H, Watkins DN, Jair KW, et al. Epigenetic inactivation of SFRP genes allows constitutiveWNTsignaling in colorectal cancer. Nat Genet. 2004; 36: 417-422.
52. Issa JP. Cancer prevention: epigenetics steps up to the plate. Cancer Prev Res (Phila Pa). 2008;1:219-222.
53. Ushijima T. Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer. 2005;5:223-231.
54. Shen L, Kondo Y, Rosner GL, et al. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst. 2005;97:1330-1338.
55. Aggerholm A, Guldberg P, Hokland M, Hokland P. Extensive intra- and interindividual heterogeneity of p15INK4B methylation in acute myeloid leukemia. Cancer Res. 1999;59:436-441.
56. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad SciUSA. 1999; 96: 8681-8686.
57. Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci U S A. 2007;104:18654-18659.
58. Lapeyre JN, Becker FF. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun. 1979;87:698-705.
59. Feinberg AP, Gehrke CW, Kuo KC, Ehrlich M. Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 1988;48:1159-1161.
60. Estecio MR, Gharibyan V, Shen L, et al. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability. PLoS One. 2007; 2: e399.
61. Dunn BK. Hypomethylation: one side of a larger picture. AnnNY Acad Sci. 2003;983: 28-42.
62. Chen RZ, Pettersson U, Beard C, Jackson- Grusby L, Jaenisch R. DNA hypomethylation leads to elevated mutation rates. Nature. 1998;395:89-93.
63. Issa JP. Colon cancer: it's CIN or CIMP. Clin Cancer Res. 2008;14:5939-5940.
64. Ogino S, Nosho K, Kirkner GJ. et al. Acohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst. 2008;100:1734-1738.
65. Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene. 2002;21:5400-5413.
66. Trinh BN, Long TI, Nickel AE, Shibata D, Laird PW. DNA methyltransferase deficiency modifies cancer susceptibility in mice lacking DNA mismatch repair. Mol Cell Biol. 2002;22:2906-2917.
67. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300:455.
68. Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358:1148-1159.
69. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8:286-298.
70. Widschwendter M, Fiegl H, Egle D, et al. Epigenetic stem cell signature in cancer. Nat Genet. 2007;39:157-158.
71. Bannister AJ, Schneider R, Kouzarides T. Histone methylation: dynamic or static? Cell. 2002;109:801-806.
72. Cao R, Wang L, Wang H, et al. Role of histone H3 lysine 27 methylation in Polycomb- group silencing. Science. 2002;298: 1039-1043.
73. Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 2003;100:11606-11611.
74. Martinez-Garcia E, Licht JD. Deregulation of H3K27 methylation in cancer. Nat Genet. 2010;42:100-101.
75. Yu J, Rhodes DR, Tomlins SA, et al. A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res. 2007;67:10657-10663.
76. Kondo Y, Shen L, Cheng AS, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNAmethylation. Nat Genet. 2008; 40: 741-750.
77. Morin RD, Johnson NA, Severson TM. et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42:181-185.
78. van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41:521-523.
79. Keats JJ, Maxwell CA, Taylor BJ. et al. Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32) -positive multiple myeloma patients. Blood. 2005; 105: 4060-4069.
80. Peters AH, O'Carroll D, Scherthan H, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107: 323-337.
81. Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T. AML with 11q23/MLL abnormalities as defined by theWHOclassification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzedAML cases. Blood. 2003;102:2395-2402.
82. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41-47.
83. Carbone R, Botrugno OA, Ronzoni S, et al. Recruitment of the histone methyltransferase SUV39H1 and its role in the oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion protein. Mol Cell Biol. 2006;26:1288-1296.
84. Segalla S, Rinaldi L, Kilstrup-Nielsen C. et al. Retinoic acid receptor alpha fusion to PML affects its transcriptional and chromatin- remodeling properties. Mol Cell Biol. 2003;23:8795-8808.
85. Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 2000;14:1553-1577.
86. Iyer NG, Ozdag H, Caldas C. p300/CBP and cancer. Oncogene. 2004; 23: 4225-4231.
87. Deng Q, Li Y, Tedesco D, Liao R, Fuhrmann G, Sun P. The ability of E1A to rescue ras-induced premature senescence and confer transformation relies on inactivation of both p300/CBP and Rb family proteins. Cancer Res. 2005;65:8298-8307.
88. Neff T, Armstrong SA. Chromatin maps, histone modifications and leukemia. Leukemia. 2009;23:1243-1251.
89. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294:858-862.
90. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853-858.
91. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25-36.
92. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7RNAregulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901-906.
93. Hipfner DR, Weigmann K, Cohen SM. The bantam gene regulates Drosophila growth. Genetics. 2002;161:1527-1537.
94. Kanellopoulou C, Muljo SA, Kung AL, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 2005;19: 489-501.
95. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857-866.
96. Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009; 8: 843-852.
97. Cimmino A, Calin GA, Fabbri M. et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944-13949.
98. Olive V, Jiang I, He L. mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 2010;42: 1348-1354.
99. Inomata M, Tagawa H, Guo YM, Kameoka Y, Takahashi N, Sawada K. MicroRNA- 17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. Blood. 2009;113:396-402.
100. Xiao C, Srinivasan L, Calado DP, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9:405-414.
101. Mu P, Han YC, Betel D, et al. Genetic dissection of the miR-17_92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 2009;23:2806-2811.
102. Merritt WM, Lin YG, Han LY, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008;359: 2641-2650.
103. Colella S, Shen L, Baggerly KA, Issa JP, Krahe R. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques. 2003; 35: 146-150.
104. Cottrell SE, Laird PW. Sensitive detection of DNA methylation. Ann N Y Acad Sci. 2003;983:120-130.
105. Li M, Chen WD, Papadopoulos N, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009;27:858-863.
106. Cairns P, Esteller M, Herman JG, et al. Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clin Cancer Res. 2001;7:2727-2730.
107. Lee WH, Morton RA, Epstein JI, et al. Cytidine methylation of regulatory sequences near the pi-class glutathione Stransferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci U S A. 1994;91:11733-11737.
108. Jarmalaite S, Jankevicius F, Kurgonaite K, Suziedelis K, Mutanen P, Husgafvel- Pursiainen K. Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer. Oncology. 2008; 75: 145-151.
109. Catto JW, Azzouzi AR, Rehman I, et al. Promoter hypermethylation is associated with tumor location, stage, and subsequent progression in transitional cell carcinoma. J Clin Oncol. 2005;23:2903-2910.
110. 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.
111. Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343:1350-1354.
112. Issa JP, Shen L, Toyota M. CIMP, at last. Gastroenterology. 2005; 129: 1121-1124.
113. Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004; 4: 988-993.
114. Shen L, Issa JP. Epigenetics in colorectal cancer. Curr Opin Gastroenterol. 2002;18: 68-73.
115. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17: 510-522.
116. Abe M, Ohira M, Kaneda A, et al. CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas. Cancer Res. 2005;65:828-834.
117. Brock MV, Hooker CM, Ota-Machida E, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008;358:1118-1128.
118. Belinsky SA, Klinge DM, Dekker JD, et al. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res. 2005;11:6505-6511.
119. Hoque MO, Begum S, Topaloglu O, et al. Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst. 2006; 98:996-1004.
120. Seligson DB, Horvath S, Shi T, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 2005;435:1262-1266.
121. Marcucci G, Radmacher MD, Maharry K, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1919-1928.
122. Eilers T, Machtens S, Tezval H, et al. Prospective diagnostic efficiency of biopsy washing DNA GSTP1 island hypermethylation for detection of adenocarcinoma of the prostate. Prostate. 2007;67:757-763.
123. Shen L, Kantarjian H, Guo Y, et al. DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. J Clin Oncol. 2010; 28:605-613.
124. Belinsky SA, Liechty KC, Gentry FD, et al. Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 2006;66:3338-3344.
125. Dobrovic A, Kristensen LS. DNA methylation, epimutations and cancer predisposition. Int J Biochem Cell Biol. 2009; 41: 34-39.
126. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1-18.
127. Hitchins MP, Ward RL. Constitutional (germline) MLH1 epimutation as an aetiological mechanism for hereditary nonpolyposis colorectal cancer. J Med Genet. 2009;46:793-802.
128. Ligtenberg MJ, Kuiper RP, Chan TL, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3_ exons of TACSTD1. Nat Genet. 2009;41: 112-117.
129. Boumber YA, Kondo Y, Chen X, et al. An Sp1/Sp3 binding polymorphism confers methylation protection. PLoS Genet. 2008; 4:e1000162.
130. Palmisano WA, Divine KK, Saccomanno G, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 2000;60:5954-5958.
131. Cui H, Cruz-Correa M, Giardiello FM, et al. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science. 2003;299: 1753-1755.
132. Chen WD, Han ZJ, Skoletsky J, et al. Detection in fecal DNA of colon cancerspecific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst. 2005;97: 1124-1132.
133. Rosenfeld N, Aharonov R, Meiri E. et al. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008; 26: 462-469.
134. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353: 1793-1801.
135. Raponi M, Dossey L, Jatkoe T, et al. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 2009;69:5776-5783.
136. Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005;102:3627-3632.
137. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005;10:176-182.
138. Fenaux P, Mufti GJ, Hellstrom-Lindberg E. et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009; 10: 223-232.
139. Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higherrisk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109: 52-57.
140. Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007;12:1247-1252.
141. Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009; 27: 5410-5417.
142. Issa JP, Kantarjian HM. Targeting DNA methylation. Clin Cancer Res. 2009;15: 3938-3946.
143. Von Hoff DD, Slavik M, Muggia FM. 5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. Ann Intern Med. 1976; 85: 237-245.
144. 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.
145. Kaminskas E, Farrell A, Abraham S. et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res. 2005; 11: 3604-3608.
146. Gore SD, Jones C, Kirkpatrick P. Decitabine. Nat Rev Drug Discov. 2006;5:891-892.
147. Kantarjian HM, O'Brien S, Huang X, et al. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer. 2007;109:1133-1137.
148. Datta J, Ghoshal K, Denny WA, et al. A new class of quinoline-basedDNAhypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res. 2009;69:4277-4285.
149. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007; 26: 5541-5552.
150. Prince HM, Bishton MJ, Harrison SJ. Clinical studies of histone deacetylase inhibitors. Clin Cancer Res. 2009;15:3958-3969.
151. Yao X, Hu JF, Daniels M, et al. A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma. J Clin Invest. 2003;111:265-273.
152. Kim MS, Blake M, Baek JH, Kohlhagen G, Pommier Y, Carrier F. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 2003;63:7291-7300.
153. Issa JP, Gharibyan V, Cortes J, et al. Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J Clin Oncol. 2005;23:3948-3956.
154. Blum W, Klisovic RB, Hackanson B, et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol. 2007;25: 3884-3891.
155. Link PA, Baer MR, James SR, Jones DA, Karpf AR. p53-inducible ribonucleotide reductase (p53R2/RRM2B) is a DNA hypomethylation- independent decitabine gene target that correlates with clinical response in myelodysplastic syndrome/ acute myelogenous leukemia. Cancer Res. 2008;68:9358-9366.
156. Blum W, Garzon R, Klisovic RB, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010;107:7473-7478.
157. Qin T, Jelinek J, Si J, Shu J, Issa JP. Mechanisms of resistance to 5-aza-2_- deoxycytidine in human cancer cell lines. Blood. 2009;113:659-667.
158. Kakihara T, Fukuda T, Tanaka A, et al. Expression of deoxycytidine kinase (dCK) gene in leukemic cells in childhood: decreased expression of dCK gene in relapsed leukemia. Leuk Lymphoma. 1998; 31:405-409.
159. Sebastiani V, Ricci F, Rubio-Viqueira B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res. 2006;12: 2492-2497.
160. Schaefer M, Hagemann S, Hanna K, Lyko F. Azacytidine inhibits RNA methylation at DNMT2 target sites in human cancer cell lines. Cancer Res. 2009;69:8127-8132.