Abstract
Cancer has been considered a genetic disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. Of late, aberrant epigenetic modifications have been elucidated in cancer, and together with genetic alterations, they have been helpful in understanding the complex traits observed in neoplasia. “Cancer Epigenetics” therefore has contributed substantially towards understanding the complexity and diversity of various cancers. However, the positioning of epigenetic events during cancer progression is still not clear, though there are some reports implicating aberrant epigenetic modifications in very early stages of cancer. Amongst the most studied aberrant epigenetic modifications are the DNA methylation differences at the promoter regions of genes affecting their expression. Hypomethylation mediated increased expression of oncogenes and hypermethylation mediated silencing of tumor suppressor genes are well known examples. This chapter also explores the correlation of DNA methylation and demethylation enzymes with cancer.
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Adorjan P, Distler J, Lipscher E, Model F, Muller J, Pelet C, Braun A, Florl AR, Gutig D, Grabs G et al (2002) Tumor class prediction and discovery by microarray-based DNA methylation analysis. Nucleic Acids Res 30:e21
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP (1998) Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 58:5489–5494
Akiyama Y, Maesawa C, Ogasawara S, Terashima M, Masuda T (2003) Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells. Am J Pathol 163:1911–1919
Amara K, Ziadi S, Hachana M, Soltani N, Korbi S, Trimeche M (2010) DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas. Cancer Sci 101:1722–1730
Amatya VJ, Naumann U, Weller M, Ohgaki H (2005) TP53 promoter methylation in human gliomas. Acta Neuropathol (Berl) 110:178–184
Arima T, Hata K, Tanaka S, Kusumi M, Li E, Kato K, Shiota K, Sasaki H, Wake N (2006) Loss of the maternal imprint in DNMT3L mat−/− mice leads to a differentiation defect in the extraembryonic tissue. Dev Biol 297:361–373
Baba S, Yamada Y, Hatano Y, Miyazaki Y, Mori H, Shibata T, Hara A (2009) Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus. Cancer Sci 100:1186–1191
Badal V, Chuang LS, Tan EH, Badal S, Villa LL, Wheeler CM, Li BF, Bernard HU (2003) CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimen: genomic hypomethylation correlates with carcinogenic progression. J Virol 77:6227–6234
Ballestar E, Esteller M (2005) Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger. Biochem Cell Biol 83:374–384
Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer: a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116
Baylin SB, Hoppener JW, de Bustros A, Steenbergh PH, Lips CJ, Nelkin BD (1986) DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas. Cancer Res 46:2917–2922
Belinsky SA, Nikula KJ, Baylin SB, Issa JP (1996) Increased cytosine DNA-methyltransferase activity is target-cell-specific and an early event in lung cancer. Proc Natl Acad Sci USA 93:4045–4050
Belinsky SA, Nikulan KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG (1998) Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA 95:11891–11896
Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463:1042–1047
Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21
Bird AP, Wolffe AP (1999) Methylation-induced repression-Belts, braces, and chromatin. Cell 99:451–454
Bogdanović O, Veenstra GJ (2009) DNA methylation and methyl-CpG binding proteins: developmental requirements and functions. Chromosoma 118:549–565
Bourc’his C, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–2539
Burgers WA, Fuks F, Kouzarides T (2002) DNA methyltransferases get connected to chromatin. Trends Genet 18:275–277
Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gökbuget N et al (2009) The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood 113:4011–4015
Buschhausen G, Wittig B, Graessmann M, Graessmann A (1987) Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci USA 84:1177–1181
Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21:103–107
Cebrian A, Pharoah PD, Ahmed S, Ropero S, Fraga MF, Smith PL, Conroy D, Luben R, Perkins B, Easton DF et al (2006) Genetic variants in epigenetic genes and breast cancer risk. Carcinogenesis 27:1661–1669
Champion C, Guianvarc’h D, Senamaud-Beaufort C, Jurkowska RZ, Jeltsch A, Ponger L, Arimondo PB, Guieysse-Peugeot AL (2010) Mechanistic insights on the inhibition of c5 DNA methyltransferases by zebularine. PLoS One 5:e12388
Chanda S, Dasgupta UB, Guhamazumder D, Gupta M, Chaudhuri U, Lahiri S, Das S, Ghosh N, Chatterjee D (2006) DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy. Toxicol Sci 89:431–437
Chatagnon A, Bougel S, Perriaud L, Lachuer J, Benhattar J, Dante R (2009) Specific association between the methyl-CpG-binding domain protein 2 and the hypermethylated region of the human telomerase reverse transcriptase promoter in cancer cells. Carcinogenesis 30:28–34
Chedin F, Lieber MR, Hsieh CL (2002) The DNA methyltransferases-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci USA 99:16916–16921
Cheng JC, Yoo CB, Weisenberger DJ, Chuang J, Wozniak C, Liang G, Marquez VE, Greer S, Orntoft TF, Thykjaer T, Jones PA (2004) Preferential response of cancer cells to zebularine. Cancer Cell 6:151–158
Cho M, Uemura H, Kim SC, Kawada Y, Yoshida K, Hirao Y, Konishi N, Saga S, Yoshikawa K (2001) Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma. Br J Cancer 85:563–567
Cho YH, Yazici H, Wu HC, Terry MB, Gonzalez K, Qu M, Dalay N, Santella RM (2010) Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients. Anticancer Res 30:2489–2496
Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, Qiu X, Yoo CB, Jones PA (2010) S110, a 5-aza-2′-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther 9:1443–1450
Clark SJ (2007) Action at a distance: epigenetic silencing of large chromosomal regions in carcinogenesis. Hum Mol Genet 16(Spec No 1):R88–R95
Cohen Y, Singer G, Lavie O, Dong SM, Beller U, Sidransky D (2003) The RASSF1A tumor suppressor gene is commonly inactivated in adenocarcinoma of the uterine cervix. Clin Cancer Res 9:2981–2984
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867
Dadkalos A, Oleksiewicz U, Filia A, Nikolaidis G, Xinarianos G, Gosney JR, Malliri A, Field JK, Liloglou T (2011) UHRF1-mediated tumor suppressor gene inactivation in nonsmall cell lung cancer. Cancer 117:1027–1037
Dahl C, Grønbæk K, Guldberg P (2011) Advances in DNA methylation: 5-hydroxymethylcytosine revisited. Clin Chim Acta. doi:10.1016/j.cca.2011.02.013
Dammann RH, Kirsch S, Schagdarsurengin U, Dansranjavin T, Gradhand E, Schmitt WD, Hauptmann S (2010) Frequent aberrant methylation of the imprinted IGF2/H19 locus and LINE1 hypomethylation in ovarian carcinoma. Int J Oncol 36:171–179
Dandrea M, Donadelli M, Costanzo C, Scarpa A, Palmieri M (2009) MeCP2/H3meK9 are involved in IL-6 gene silencing in pancreatic adenocarcinoma cell lines. Nucleic Acids Res 37:6681–6690
Datta J, Ghoshal K, Sharma SM, Tajima S, Jacob ST (2003) Biochemical fractionation reveals association of DNA methyltransferase (Dnmt)3b with Dnmt1 and that of Dnmt 3a with a histone H3 methyltransferase and Hdac1. J Cell Biochem 88:855–864
De Capoa A, Musolino A, Della Rosa S, Caiafa P, Mariani L, Del Nonno F, Vocaturo A, Donnorso RP, Niveleau A, Grappelli C (2003) DNA demethylation is directly related to tumor progression: evidence in normal, pre-malignant and malignant cells from uterine cervix samples. Oncol Rep 10:545–549
De Marzo AM, Marchi VL, Yang ES, Veeraswamy R, Lin X, Nelson WG (1999) Abnormal regulation of DNA methyltransferase expression during colorectal carcinogenesis. Cancer Res 59:3855–3860
Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C et al (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295:1079–1082
Diede SJ, Guenthoer J, Geng LN, Mahoney SE, Marotta M, Olson JM, Tanaka H, Tapscott SJ (2010) DNA methylation of developmental genes in pediatric medulloblastomas identified by denaturation analysis of methylation differences. Proc Natl Acad Sci USA 107:234–239
Dodge JE, Okano M, Dick F, Tsujimoto N, Chen T, Wang S, Ueda Y, Dyson N, Li E (2005) Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization. J Biol Chem 280:17986–17991
Doherty AS, Bartolomei MS, Schultz RM (2002) Regulation of stage-specific nuclear translocation of Dnmt1o during preimplantation mouse development. Dev Biol 242:255–266
Duncan BK, Miller JH (1980) Mutagenic deamination of cytosine residues in DNA. Nature 287:560–561
Dutrillaux B, Gerbault-Seureau M, Remvikos Y, Zafrani B, Prieur M (1991) Breast cancer genetic evolution: data from cytogenetics and DNA content. Breast Cancer Res Treat 193:245–255
Eads CA, Nickel AE, Laird PW (2002) Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice. Cancer Res 62:1296–1299
Eden A, Gaudet F, Waghmare A, Jaenisch R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455
Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463
Ehrlich M (2009) DNA hypomethylation in cancer cells. Epigenomics 1:239–259
Endo Y, Marusawa H, Chiba T (2011) Involvement of activation-induced cytidine deaminase in the development of colitis-associated colorectal cancers. J Gastroenterol 46(Suppl 1):6–10
Esteller M (2005) Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 45:629–656
Esteller M (2006) The necessity of a human epigenome project. Carcinogenesis 27:1121–1125
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298
Ezzikouri S, El Feydi AE, Benazzouz M, Afifi R, El Kihal L, Hassar M, Akil A, Pineau P, Benjelloun S (2009) Single nucleotide polymorphism in DNMT3B promoter and its association with hepatocellular carcinoma in a Moroccan population. Infect Genet Evol 9:877–881
Fabris S, Bollati V, Agnelli L, Morabito F, Motta V, Cutrona G, Matis S, Recchia AG, Gigliotti V, Gentile M et al (2011) Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia. Epigenetics 6:188–194
Fan T, Yan Q, Huang J, Austin S, Cho E, Ferris D, Muegge K (2003) Lsh-deficient murine embryonal fibroblasts show reduced proliferation with signs of abnormal mitosis. Cancer Res 63:4677–4683
Fazzari MJ, Greally JM (2004) Epigenomics: beyond CpG islands. Nat Rev Genet 5:446–455
Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153
Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92
Feinberg AP, Ghrke CW, Kuo KC, Ehrlich M (1988) Reduced genomic 5-methylcytosine genomic content in human colonic neoplasia. Cancer Res 48:1159–1161
Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33
Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF et al (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567
Frigola J, Song J, Stirzaker C, Hinshelwood RA, Peinado MA, Clark SJ (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat Genet 38:540–549
Gal-Yam EN, Saito Y, Egger G, Jones PA (2008) Cancer epigenetics: modifications, screening, and therapy. Annu Rev Med 59:267–280
Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW, Ehrlich M (1983) The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res 11:6883–6894
Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G (2009) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113:6411–6418
Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, Leonhardt H, Jaenisch R (2003) Induction of tumors in mice by genomic hypomethylation. Science 300:489–492
Gibbons RJ, McDowell TL, Raman S, O’Rourke DM, Garrick D, Ayyub H, Higgs DR (2000) Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat Genet 24:368–371
Girault I, Tozlu S, Lidereau R, Bieche I (2003) Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin Cancer Res 9:4415–4422
Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP (1985) Hypomethylation of DNA from benign and malignant human colon neoplasm’s. Science 228:187–190
Gokul G, Gautami B, Malathi S, Sowjanya AP, Poli UR, Jain M, Ramakrishna G, Khosla S (2007) DNA methylation profile at the DNMT3L promoter: a potential biomarker for cervical cancer. Epigenetics 2:80–85
Gokul G, Ramakrishna G, Khosla S (2009) Reprogramming of HeLa cells upon DNMT3L overexpression mimics carcinogenesis. Epigenetics 4:322–329
Gotze S, Feldhaus V, Traska T, Wolter M, Reifenberger G, Tannapfel A, Kuhnen C, Martin D, Muller O, Sievers S (2009) ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma. BMC Cancer 9:447
Gowher H, Liebert K, Hermann A, Xu G, Jeltsch A (2005) Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem 280:13341–13348
Grandjean V, Yaman R, Cuzin F, Rassoulzadegan M (2007) Inheritance of an epigenetic mark: the CpG DNA methyltransferase1 is required for de novo establishment of a complex pattern of non-CpG methylation. PLoS One 2:e1136
Greger V, Passarge E, Hopping W, Messmer E, Horsthemke B (1989) Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet 83:155–158
Hirasawa R, Feil R (2010) Genomic imprinting and human disease. Essays Biochem 48:187–200
Hu J, Fan H, Liu D, Zhang S, Zhang F, Xu H (2010) DNMT3B promoter Polymorphism and risk of gastric cancer. Dig Dis Sci 55:1011–1016
Iqbal K, Jin SG, Pfeifer GP, Szabó PE (2011) Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci USA 108:3642–3647
Issa JP (2003) Methylation and prognosis: of molecular clocks and hypermethylator phenotypes. Clin Cancer Res 9:2879–2881
Issa JP (2004) CpG island methylator phenotype in cancer. Nat Rev Cancer 4:988–993
Issa JP (2007) DNA methylation as a therapeutic target in cancer. Clin Cancer Res 13:1634–1637
Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, Nelkin BD, Hamilton SR, Baylin SB (1993) Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Natl Cancer Inst 85:1235–1240
Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540
Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:1129–1133
Jacinto FV, Esteller M (2007) Mutator pathways unleashed by epigenetic silencing in human cancer. Mutagenesis 22:247–253
Jair KW, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen RW, Baylin SB, Schuebel KE (2006) De novo CpG island methylation in human cancer cells. Cancer Res 66:682–692
Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT (2006) Stem cell ageing modified by the cyclin-dependent kinase inhibitor p16(INK4a). Nature 443:421–426
Jelinic P, Shaw P (2007) Loss of imprinting and cancer. J Pathol 211:261–268
Jirtle RL (1999) Genomic imprinting and cancer. Exp Cell Res 248:18–24
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428
Jones PA, Gonzalgo ML (1997) Altered DNA methylation and genome instability: a new pathway to cancer? Proc Natl Acad Sci USA 94:2103–2105
Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191
Juhlin CC, Kiss NB, Villablanca A, Haglund F, Nordenstrom J, Hoog A, Larsson C (2010) Frequent promoter hypermethylation of the APC and RASSF1A tumor suppressors in parathyroid tumors. PLoS One 5:e9472
Juttermann R, Li E, Jaenisch R (1994) Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA 91:11797–11801
Kanai Y (2008) Alterations of DNA methylation and clinicopathological diversity of human cancers. Pathol Int 58:544–558
Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429:900–903
Kareta MS, Botello ZM, Ennis JJ, Chou C, Chedin F (2006) Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. J Biol Chem 281:25893–25902
Keshet I, Lieman-Hurwitz J, Cedar H (1986) DNA methylation affects the formation of active chromatin. Cell 44:535–543
Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (2002) Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 21:4183–4195
Kim MJ, White-Cross JA, Shen L, Issa JP, Rashid A (2009) Hypomethylation of long interspersed nuclear element-1 in hepatocellular carcinomas. Mod Pathol 22:442–449
Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396:84–88
Klemm L, Duy C, Iacobucci I, Kuchen S, von Levetzow G, Feldhahn N, Henke N, Li Z, Hoffmann TK, Kim YM, Hofmann WK, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber MR, Casellas R, Müschen M (2009) The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 16:232–245
Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31:89–97
Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823
Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R, Liu XS et al (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468:839–843
Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930
Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE (2006) P16(INK4a) induces an age-independent decline in islet regenerative potential. Nature 443:453–457
Krivtsov AV, Armstrong SA (2007) MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7:823–833
Kwa FA, Balcerczyk A, Licciardi P, El-Osta A, Karagiannis TC (2011) Chromatin modifying agents – the cutting edge of anticancer therapy. Drug Discov Today 16:543–547
Lacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R et al (2003) Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol 162:1151–1162
Laird PW (2003) The power and the promise of DNA methylation markers. Nat Rev Cancer 3:253–266
Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, Li E, Weinberg RA, Jaenisch R (1995) Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81:197–205
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921
Langemeijer SM, Jansen JH, Hooijer J, van Hoogen P, Stevens-Linders E, Massop M, Waanders E, van Reijmersdal SV, Stevens-Kroef MJ, Zwaan CM et al (2011) TET2 mutations in childhood leukemia. Leukemia 25:189–192
Larsen F, Gundersen G, Prydz H (1992) Choice of enzymes for mapping based on CpG islands in the human genome. Genet Anal Tech Appl 9:80–85
Lei H, Oh SP, Okano M, Jüttermann R, Goss KA, Jaenisch R, Li E (1996) De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122:3195–3205
Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926
Li S, Chiang TC, Richard-Davis G, Barrett JC, Mclachlan JA (2003) DNA hypomethylation and imbalanced expression of DNA methyltransferases (DNMT1, 3A, and 3B) in human uterine leiomyoma. Gynecol Oncol 90:123–130
Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR (2003) TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 17:637–641
Loshikhes IP, Zhang MQ (2000) Large-scale human promoter mapping using CpG islands. Nat Genet 26:61–63
Lu H, Ouyang W, Huang C (2006) Inflammation, a key event in cancer development. Mol Cancer Res 4:221–233
Magdinier F, Wolffe AP (2001) Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasia. Proc Natl Acad Sci USA 98:4990–4995
Manderwad GP, Gokul G, Kannabiran C, Honavar SG, Khosla S, Vemuganti G (2010) Hypomethylation of the DNMT3L promoter in Ocular Surface Squamous Neoplasia (OSSN). Arch Pathol Lab Med 134:1193–1196
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715
Martin V, Jorgensen HF, Chaubert AS, Berger J, Barr H, Shaw P, Bird A, Chaubert P (2008) MBD2-mediated transcriptional repression of the p14ARF tumor suppressor gene in human colon cancer cells. Pathobiology 75:281–287
Marusawa H, Chiba T (2010) Helicobacter pylori-induced activation-induced cytidine deaminase expression and carcinogenesis. Curr Opin Immunol 22:442–447
Matousova M, Votruba I, Otmar M, Tloustova E, Gunterova J, Mertlikova-kaiserova H (2011) 2′-deoxy-5,6-dihydro-5-azacytidine – a less toxic alternative of 2′-deoxy-5-azacytidine: a comparative study of hypomethylating potential. Epigenetics 6:769–776
Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, Azuma T, Okazaki IM, Honjo T, Chiba T (2007) Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med 13:470–476
Matsumoto Y, Marusawa H, Kinoshita K, Niwa Y, Sakai Y, Chiba T (2010) Up-regulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. Gastroenterology 139:1984–1994
Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000) Demethylation of the zygotic paternal genome. Nature 403:501–502
Melki JR, Warnecke P, Vincent PC, Clark SJ (1998) Increased DNA methyltransferase expression in leukaemia. Leukemia 12:311–316
Minami K, Chano T, Kawakami T, Ushida H, Kushima R, Okabe H, Okada Y, Okamoto K (2010) DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma. Clin Cancer Res 16:2751–2759
Miremadi A, Oestergaard MZ, Pharoah PD, Caldas C (2007) Cancer genetics of epigenetic genes. Hum Mol Genet 16(Spec No 1):R28–R49
Missaoui N, Hmissa S, Dante R, Frappart L (2010) Global DNA methylation in precancerous and cancerous lesions of the uterine cervix. Asian Pac J Cancer Prev 11:1741–1744
Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ (2006) Increasing p16(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–452
Momparler RL, Ayoub J (2001) Potential of 5-aza-2′-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. Lung Cancer 34(Suppl 4):S111–S1115
Momparler RL, Bovenzi V (2000) DNA methylation and cancer. J Cell Physiol 183:145–154
Momparler RL, Bouchard J, Samson J (1985) Induction of differentiation and inhibition of DNA methylation in HL-60 myeloid leukemic cells by 5-AZA-2′-deoxycytidine. Leuk Res 9:1361–1366
Momparler RL, Rossi M, Bouchard J, Bartolucci S, Momparler LF, Raia CA, Nucci R, Vaccaro C, Sepe S (1986) 5-Aza-2′-deoxycytidine synergistic action with thymidine on leukemic cells and interaction of 5-AZA-dCMP with dCMP deaminase. Adv Exp Med Biol 195 Pt B:157–163
Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279:52353–52360
Muller HM, Fiegl H, Goebel G, Hubalek MM, Widschwendter A, Muller-Holzner E, Marth C, Widschwendter M (2003) MeCP2 and MBD2 expression in human neoplastic and non-neoplastic breast tissue and its association with oestrogen receptor status. Br J Cancer 89:1934–1939
Murchie AI, Lilley DM (1989) Base methylation and local DNA helix stability. Effect on the kinetics of cruciform extrusion. J Mol Biol 205:593–602
Nakamura N, Takenaga K (1998) Hypomethylation of the metastasis-associated S100A4 gene correlates with gene activation in human colon adenocarcinoma cell lines. Clin Exp Metastasis 16:471–479
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389
Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB (2004) The role of inflammation in the pathogenesis of prostate cancer. J Urol 172:S6–S11
Neumeister P, Albanese C, Balent B, Greally J, Pestell RG (2002) Senescence and epigenetic dysregulation in cancer. Int J Biochem Cell Biol 34:1475–1490
Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999) MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 23:58–61
Nguyen CT, Weisenberger DJ, Velicescu M, Gonzales FA, Lin JC, Liang G, Jones PA (2002) Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2’-deoxycytidine. Cancer Res 62:6456–6461
Nuovo GJ, Plaia TW, Belinsky SA, Baylin SB, Herman JG (1999) In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proc Natl Acad Sci USA 96:12754–12759
O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumor growth in immunodeficient mice. Nature 445:106–110
Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, Giovannucci EL, Fuchs CS (2008) A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst 100:1734–1738
Ohm JE, Baylin SB (2007) Stem cell chromatin patterns: an instructive mechanism for DNA hypermethylation? Cell Cycle 6:1040–1043
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257
Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y (2002) 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 62:4075–4080
Ooi SK, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133:1145–1148
Ooi SK, Qui C, Bernstein E, Li K, Jia D, Yang Z, Erdjument-Bromage H, Tempst P, Lin SP, Allis CD, Cheng X, Bestor TH (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714–717
Ooi SK, Wolf D, Hartung O, Agarwal S, Daley GQ, Goff SP, Bestor TH (2010) Dynamic instability of genomic methylation patterns in pluripotent stem cells. Epigenet Chromatin 3:17
Oshimo Y, Nakayama H, Ito R, Kitadai Y, Yoshida K, Chayama K, Yasui W (2003) Promoter methylation of cyclin D2 gene in gastric carcinoma. Int J Oncol 6:1663–1670
Pancione M, Sabatino L, Fucci A, Carafa V, Nebbioso A, Forte N, Febbraro A, Parente D, Ambrosino C, Normanno N, Altucci L, Colantuoni V (2010) Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients’ outcome. PLoS One 5:e14229
Pinto A, Zagonel V (1993) 5-Aza-2′-deoxycytidine (Decitabine) and 5-azacytidine in the treatment of acute myeloid leukemias and myelodysplastic syndromes: past, present and future trends. Leukemia 7(Suppl 1):51–60
Pinto A, Attadia V, Fusco A, Ferrara F, Spada OA, Di Fiore PP (1984) 5-Aza-2′-deoxycytidine induces terminal differentiation of leukemic blasts from patients with acute myeloid leukemias. Blood 64:922–929
Pitot HC (1986) Oncogenes and human neoplasia. Clin Lab Med 6:167–179
Piyathilake CJ, Henao O, Frost AR, Macaluso M, Bell WC, Johanning GL, Heimburger DC, Niveleau A, Grizzle WE (2003) Race- and age-dependent alterations in global methylation of DNA in squamous cell carcinoma of the lung (United States). Cancer Causes Control 14:37–42
Ponger L, Duret L, Mouchiroud D (2001) Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 11:1854–1860
Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, Jacobsen SE, Reik W (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463:1101–1105
Prokhortchouk A, Hendrich B, Jørgensen H, Ruzov A, Wilm M, Georgiev G, Bird A, Prokhortchouk E (2001) The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev 15:1613–1618
Prokhortchouk A, Sansom O, Selfridge J, Caballero IM, Salozhin S, Aithozhina D, Cerchietti L, Meng FG, Augenlicht LH, Mariadason JM et al (2006) Kaiso-deficient mice show resistance to intestinal cancer. Mol Cell Biol 26:199–208
Qu GZ, Grundy PE, Narayan A, Ehrlich M (1999) Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16. Cancer Genet Cytogenet 109:34–39
Qu Y, Mu G, Wu Y, Dai X, Zhou F, Xu X, Wang Y, Wei F (2010) Overexpression of DNA methyltransferases 1, 3a, and 3b significantly correlates with retinoblastoma tumorigenesis. Am J Clin Pathol 134:826–834
Radpour R, Barekati Z, Kohler C, Lv Q, Burki N, Diesch C, Bitzer J, Zheng H, Schmid S, Zhong XY (2011) Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer. PLoS One 6:e16080
Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008) DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135:1201–1212
Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R (2000) Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci USA 97:5237–5242
Ren R (2005) Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 5:172–183
Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A et al (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102:565–575
Reynolds PA, Sigaroudinia M, Zardo G, Wilson MB, Benton GM, Miller CJ, Hong C, Fridlyand J, Costello JF, Tlsty TD (2006) Tumor suppressor P16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. J Biol Chem 281:24790–24802
Rhee I, Jair KW, Yen RW, Lengauer C, Herman JG, Kinzler KW, Vogelstein B, Baylin SB, Schuebel KE (2000) CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404:1003–1007
Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (2002) DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416:552–556
Riggs AD, Jones PA (1983) 5-methylcytosine, gene regulation, and cancer. Adv Cancer Res 40:1–30
Rishi V, Bhattacharya P, Chatterjee R, Rozenberg J, Zhao J, Glass K, Fitzgerald P, Vinson C (2010) CpG methylation of half-CRE sequences creates C/EBP alpha binding sites that activate some tissue-specific genes. Proc Natl Acad Sci USA 107:20311–20316
Rivard GE, Momparler RL, Demers J, Benoit P, Raymond R, Lin K, Momparler LF (1981) Phase I study on 5-aza-2′-deoxycytidine in children with acute leukemia. Leuk Res 5:453–462
Robbiani DF, Bunting S, Feldhahn N, Bothmer A, Camps J, Deroubaix S, McBride KM, Klein IA, Stone G, Eisenreich TR et al (2009) AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol Cell 36:631–641
Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (1999) The human DNA methyltransferase (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res 27:2291–2298
Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (2002) Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis. Proc Natl Acad Sci USA 99:10060–10065
Sansom OJ, Berger J, Bishop SM, Hendrich B, Bird A, Clarke AR (2003) Deficiency of Mbd2 suppresses intestinal tumorigenesis. Nat Genet 34:145–147
Santi DV, Norment A, Garrett CE (1984) Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci USA 81:6993–6997
Sarraf SA, Stancheva I (2004) Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell 15:595–605
Sato N, Maitra A, Fukushima N, van Heek NT, Matsubayashi H, Iacobuzio-Donahue CA, Rosty C, Goggins M (2003) Frequent hyomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 63:4158–4166
Schernhammer ES, Giovannucci E, Kawasaki T, Rosner B, Fuchs CS, Ogino S (2010) Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut 59:794–799
Shih LY, Liang DC, Huang CF, Wu JH, Lin TL, Wang PN, Dunn P, Kuo MC, Tang TC (2006) AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples. Leukemia 20:604–609
Shukla V, Coumoul X, Lahusen T, Wang RH, Xu X, Vassilopoulos A, Xiao C, Lee MH, Man YG, Ouchi M, Ouchi T, Deng CX (2010) BRCA1 affects global DNA methylation through regulation of DNMT1. Cell Res 20:1201–1215
Singer J, Roberts-Ems J, Riggs AD (1979) Methylation of mouse liver DNA studied by means of the restriction enzymes MspI and HpaII. Science 203:1019–1021
Sinsheimer RL (1955) The action of pancreatic deoxyribonuclease II isomeric dinucleotides. J Biol Chem 215:579–583
Sorm F, Piskala A, Cihak A, Vesely J (1964) 5-Azacytidine, a new, highly effective cancerostatic. Experientia 20:202–203
Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Flam F, Frieman MB, Feinberg AP (2002) A genome wide screen for normally methylated human CpG islands that can identify normal imprinted genes. Genome Res 12:543–554
Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S (2004) DNMT3L stimulates the DNA methylation activity of Dnmt3a and DNMT3B through a direct interaction. J Biol Chem 279:27816–27823
Suter CM, Martin DI, Ward RL (2004) Hypomethylation of L1 retrotransposons in colorectal cancer and adjacent normal tissue. Int J Colorectal Dis 19:95–101
Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935
Takai D, Jones PA (2003) The CpG island searcher: a new WWW resource. In Silico Biol 3:235–240
Tanaka K, Appella E, Jay G (1983) Developmental activation of the H2K gene is correlated with an increase in DNA methylation. Cell 35:457–465
Ting AH, Jair KW, Suzuki H, Yen RW, Baylin SB, Schuebel KE (2004) CpG island hypermethylation is maintained in human colorectal cancer cells after RNAi-mediated depletion of DNMT1. Nat Genet 36:582–584
Ting AH, Jair KW, Schuebel KE, Baylin SB (2006a) Differential requirement for DNA methyltransferase 1 in maintaining human cancer cell gene promoter hypermethylation. Cancer Res 66:729–735
Ting AH, McGarvey KM, Baylin SB (2006b) The cancer epigenome-components and functional correlates. Genes Dev 20:3215–3231
Tomita H, Hirata A, Yamada Y, Hata K, Oyama T, Mori H, Yamashita S, Ushijima T, Hara A (2010) Suppressive effect of global DNA hypomethylation on gastric carcinogenesis. Carcinogenesis 31:1627–1633
Touati E (2010) When bacteria become mutagenic and carcinogenic: lessons from H. pylori. Mutat Res 703:66–70
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP (1999) CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 96:8681–8686
Tuck-Muller CM, Narayan A, Tsien F, Smeets DF, Sawyer J, Fiala ES, Sohn OS, Ehrlich M (2000) DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients. Cytogenet Cell Genet 89:121–128
Tulchinsky EM, Georgiev GP, Lukanidin EM (1996) Novel AP-1 binding site created by DNA-methylation. Oncogene 12:1737–1745
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA et al (2001) The sequence of the human genome. Science 291:1304–1351
Vertino PM, Yen RW, Gao J, Baylin SB (1996) De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase. Mol Cell Biol 16:4555–4565
Wada R, Akiyama Y, Hashimoto Y, Fukamachi H, Yuasa Y (2010) miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. Int J Cancer 127:1106–1114
Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (1999) Mi-2 complex couples DNA methylation to chromatin remodeling and histone deacetylation. Nat Genet 23:62–66
Walker BA, Wardell CP, Chiecchio L, Smith EM, Boyd KD, Neri A, Davies FE, Ross FM, Morgan GJ (2011) Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood 117:553–562
Webster KE, O’Bryan MK, Fletcher S, Crewther PE, Aapola U, Craig J, Harrison DK, Anug H, Phutikanit N, Lyle R, Meachem SJ, Antonarakis SE, de Kretser DM, Hedger MP, Peterson P, Carroll BJ, Scott HS (2005) Meiotic and epigenetic defects in DNMT3L-knockout mouse spermatogenesis. Proc Natl Acad Sci USA 102:4068–4073
Wilhelm CS, Kelsey KT, Butler R, Plaza S, Gagne L, Zens MS, Andrew AS, Morris S, Nelson HH, Schned AR, Karagas MR, Marsit CJ (2010) Implications of LINE1 methylation for bladder cancer risk in women. Clin Cancer Res 16:1682–1689
Wu SC, Zhang Y (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11:607–620
Wu J, Issa JP, Herman J, Bassett DE Jr, Nelkin BD, Baylin SB (1993) Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc Natl Acad Sci USA 90:8891–8895
Xiong Y, Dowdy SC, Xue A, Shujuan J, Eberhardt NL, Podratz KC, Jiang SW (2005) Opposite alterations of DNA methyltransferase gene expression in endometrioid and serous endometrial cancers. Gynecol Oncol 96:601–609
Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340
Yoon HF, Chan DW, Reynolds AB, Qin J, Wong J (2003) N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol Cell 12:723–734
Yoshida T, Yamashita S, Takamura-Enya T, Niwa T, Ando T, Enomoto S, Maekita T, Nakazawa K, Tatematsu M, Ichinose M, Ushijima T (2011) Alu and Satα hypomethylation in Helicobacter pylori-infected gastric mucosae. Int J Cancer 128:33–39
Yu JC, Shen CY (2002) Two-hit hypothesis of tumor suppressor gene and Revisions. J Med Sci 22:13–18
Yu S, Khor TO, Cheung KL, Li W, Wu TY, Huang Y, Foster BA, Kan YW, Kong AN (2010) Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One 5:e8579
Zacharias W, Jaworski A, Wells RD (1990) Cytosine methylation enhances Z-DNA formation in vivo. J Bacteriol 172:3278–3283
Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935
Zingg JM, Jones PA (1997) Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 18:869–882
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The basis of several sections in this manuscript was the Introduction chapter from GG’s doctoral thesis. Work in SK laboratory is supported by CDFD core support and grants from Department of Biotechnology, Government of India.
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Gokul, G., Khosla, S. (2013). DNA Methylation and Cancer. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_26
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