Epigenetic gene silencing in cancer: The DNA hypermethylome

Human Molecular Genetics

Volumn 16, Issue R1, 2007, Pages

  Esteller, Manel ^a  

^a Centro Nacional de Investigaciones Oncológicas   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; APC PROTEIN; BRCA1 PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 2B; DEATH ASSOCIATED PROTEIN KINASE; DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; HISTONE H4; HISTONE METHYLTRANSFERASE; METHYL CPG BINDING PROTEIN; METHYL CPG BINDING PROTEIN 2; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; MICRORNA; PROTEIN KINASE SYK; PROTEIN MLH1; PROTEIN P14ARF; PROTEIN P16INK4A; PROTEIN P73; RETINOBLASTOMA PROTEIN; RETINOIC ACID RECEPTOR BETA; SUPPRESSOR OF CYTOKINE SIGNALING 1; TRANSCRIPTION FACTOR GATA 4; TRANSCRIPTION FACTOR PAX6; UNINDEXED DRUG; WERNER SYNDROME PROTEIN;

AGING; ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST CANCER; CANCER; CANCER GENETICS; CARCINOGENESIS; COLON CANCER; CPG ISLAND; DIAGNOSTIC VALUE; DNA METHYLATION; DNA REPAIR; DRUG APPROVAL; DRUG TARGETING; EPIGENETICS; ESOPHAGUS CANCER; GENE INACTIVATION; GENE SILENCING; GENETIC MARKER; GLIOMA; HEAD AND NECK CANCER; HEMATOLOGIC MALIGNANCY; HUMAN; KIDNEY CANCER; LEUKEMIA; LIVER CANCER; LUNG CANCER; LYMPHOMA; NEUROBLASTOMA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PREDICTION; PRIORITY JOURNAL; REVIEW; SARCOMA; SKIN CANCER; STOMACH CANCER; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE;

AGING; CPG ISLANDS; DNA METHYLATION; EPIGENESIS, GENETIC; GENE SILENCING; GENES, TUMOR SUPPRESSOR; HUMANS; MICRORNAS; NEOPLASMS; RECQ HELICASES; RNA, NEOPLASM; WERNER SYNDROME;

EID: 34547792388     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddm018     Document Type: Review

References (99)

1. McGhee, J.D. and Ginder, G.D. (1979) Specific DNA methylation sites in the vicinity of the chicken beta-globin genes. Nature, 280, 419-420.
2. Van der Ploeg, L.H. and Flavell, R.A. (1980) DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. Cell, 4, 947-958.
3. Greger, V., Passarge, E., Hopping, W., Messmer, E. and Horsthemke, B. (1989) Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum. Genet., 83, 155-158.
4. Herman, J.G., Latif, F., Weng, Y., Lerman, M.I., Zbar, B., Liu, S., Samid, D., Duan, D.S., Gnarra, J.R., Linehan, W.M. et al. (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA, 91, 9700-9704.
5. Merlo, A., Herman, J.G., Mao, L., Lee, D.J., Gabrielson, E., Burger, P.C., Baylin, S.B. and Sidransky, D. (1995) 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/ CDKN2/MTS1 in human cancers. Nat. Med., 1, 686-692.
6. Herman, J.G., Merlo, A., Mao, L., Lapidus, R.G., Issa, J.P., Davidson, N.E., Sidransky, D. and Baylin, S.B. (1995) Inactivation of the CDKN2/ p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res., 55, 4525-4530.
7. Gonzalez-Zulueta, M., Bender, C.M., Yang, A.S., Nguyen, T., Beart, R.W., Van Tornout, J.M. and Jones, P.A. (1995) Methylation of the 5' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res., 55 4531-4535.
8. Jones, P.A. and Martienssen, R. (2005) A blueprint for a Human Epigenome Project: The AACR Human Epigenome Workshop. Cancer Res., 65, 11241-11246.
9. Esteller, M. (2006) The necessity of a human epigenome project. Carcinogenesis, 27, 1121-1125.
10. Mack, G.S. (2006) Epigenetic cancer therapy makes headway. J. Natl. Cancer Inst., 98, 1443-1444.
11. Saito, Y., Liang, G., Egger, G., Friedman, J.M., Chuang, J.C., Coetzee, G.A. and Jones, P.A. (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell, 9, 435-443.
12. Lujambio, A., Ropero, S., Ballestar, E., Fraga, M.F., Cerrato, C., Setien, F., Casado, S., Suarez-Gauthier, A., Sanchez-Cespedes, M., Gitt, A. et al. (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res., 67, 1424-1429.
13. Fraga, M.F. and Esteller, M. (2005) Towards the human cancer epigenome: a first draft of histone modifications. Cell Cycle, 4, 1377-1381.
14. Kubicek, S., Schotta, G., Lachner, M., Sengupta, R., Kohlmaier, A., Perez-Burgos, L., Linderson, Y., Martens, J.H., O'Sullivan, R.J., Fodor, B.D., Yonezawa, M., Peters, A.H. and Jenuwein, T. (2006) The role of histone modifications in epigenetic transitions during normal and perturbed development. Ernst. Schering Res. Found. Workshop, 57 1-27.
15. Fraga, M.F., Ballestar, E., Villar-Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C., Ropero, S., Petrie, K., Iyer, N.G., Perez-Rosado, A., Calvo, E., Lopez, J.A., Cano, A., Calasanz, M.J., Colomer, D., Piris, M.A., Ahn, N., Imhof, A., Caldas, C., Jenuwein, T. and Esteller, M. (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet., 37, 391-400.
16. Seligson, D.B., Horvath, S., Shi, T., Yu, H., Tze, S., Grunstein, M. and Kurdistani, S.K. (2005) Global histone modification patterns predict risk of prostate cancer recurrence. Nature, 435, 1262-1266.
17. Fraga, M.F., Ballestar, E., Paz, M.F., Ropero, S., Setien, F., Ballestar, M.L., Heine-Suner, D., Cigudosa, J.C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T.D., Wu, Y.Z., Plass, C. and Esteller, M. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl. Acad. Sci. USA, 102, 10604-10609.
18. Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V.K., Attwood, J., Burger, M., Burton, J., Cox, T.V., Davies, R., Down, T.A., Haefliger, C., Horton, R., Howe, K., Jackson, D.K., Kunde, J., Koenig, C., Liddle, J., Niblett, D., Otto, T., Pettett, R., Seemann, S., Thompson, C., West, T., Rogers, J., Olek, A., Berlin, K. and Beck, S. (2006) DNA methylation profiling of human chromosomes 6, 20 and 22. Nat. Genet., 38 1378-1385.
19. Bird, A.P. (1986) CpG-rich islands and the function of DNA methylation. Nature, 321, 209-213.
20. Futscher, B.W., Oshiro, M.M., Wozniak, R.J., Holtan, N., Hanigan, C.L., Duan, H. and Domann, F.E. (2002) Role for DNA methylation in the control of cell type specific maspin expression. Nat. Genet., 31, 175-179.
21. Khulan, B., Thompson, R.F., Ye, K., Fazzari, M.J., Suzuki, M., Stasiek, E., Figueroa, M.E., Glass, J.L., Chen, Q., Montagna, C., Hatchwell, E., Selzer, R.R., Richmond, T.A., Green, R.D., Melnick, A. and Greally, J.M. (2006) Comparative isoschizomer profiling of cytosine methylation: The HELP assay. Genome Res., 16, 1046-1055.
22. Nguyen, C., Liang, G., Nguyen, T.T., Tsao-Wei, D., Groshen, S., Lubbert, M., Zhou, J.H., Benedict, W.F. and Jones, P.A. (2001) Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells. J. Natl. Cancer Inst., 93, 1465-1472.
23. Jones, P.A. (1999) The DNA methylation paradox. Trends Genet., 15, 34-37.
24. Espada, J., Ballestar, E., Fraga, M.F., Villar-Garea, A., Juarranz, A., Stockert, J.C., Robertson, K.D., Fuks, F. and Esteller, M. (2004) Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. J. Biol. Chem., 279, 37175-37184.
25. Okano, M., Bell, D.W., Haber, D.A. and Li, E. (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99, 247-257.
26. Rhee, I., Jair, K.W., Yen, R.W., Lengauer, C., Herman, J.G., Kinzler, K.W., Vogelstein, B., Baylin, S.B. and Schuebel, K.E. (2000) CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404, 1003-1007.
27. Rhee, I., Bachman, K.E., Park, B.H., Jair, K.W., Yen, R.W., Schuebel, K.E., Cui, H., Feinberg, A.P., Lengauer, C., Kinzler, K.W., Baylin, S.B., Vogelstein, B. (2002) DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature, 416, 552-556.
28. Kim, G.D., Ni, J., Kelesoglu, N., Roberts, R.J. and Pradhan, S. (2002) Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J., 21, 4183-4195.
29. Paz, M.F., Wei, S., Cigudosa, J.C., Rodriguez-Perales, S., Peinado, M.A., Huang, T.H. and Esteller, M. (2003) Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases. Hum. Mol. Genet., 12, 2209-2219.
30. Esteller, M. (2007) Cancer epigenomics: DNA methylomes and histone modification maps. Nat. Rev. Genet., 8, doi:10.1038/nrg2005.
31. Ballestar, E. and Esteller, M. (2005) Methyl-CpG-binding proteins in cancer: Blaming the DNA methylation messenger. Biochem. Cell. Biol. 83, 374-384.
32. Fraga, M.F., Ballestar, E., Montoya, G., Taysavang, P., Wade, P.A. and Esteller, M. (2003) The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res., 31, 765-774.
33. Ballestar, E., Paz, M.F., Valle, L., Wei, S., Fraga, M.F., Espada, J., Cigudosa, J.C., Huang, T.H. and Esteller, M. (2003) Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J., 22, 6335-4635.
34. Klose, R.J., Sarraf, S.A., Schmiedeberg, L., McDermott, S.M., Stancheva, I. and Bird, A.P. (2005) DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol. Cell., 19, 667-678.
35. Lopez-Serra, L., Ballestar, E., Fraga, M.F., Alaminos, M., Setien, F. and Esteller, M. (2006) A profile of MBD protein occupancy of hypermethylated promoter CpG islands of tumor suppressor genes in human cancer. Cancer Res., 66, 8342-8346.
36. Jones, P.L., Veenstra, G.J., Wade, P.A., Vermaak, D., Kass, S.U., Landsberger, N., Strouboulis, J. and Wolffe, A.P. (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat. Genet., 19, 187-191.
37. Nan, X., Ng, H.H., Johnson, C.A., Laherty, C.D., Turner, B.M., Eisenman, R.N., Bird, A. (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature, 393, 386-389.
38. Jenuwein, T. and Allis, C.D. (2001) Translating the histone code. Science, 293, 1074-1080.
39. Turner, B.M. (2002) Cellular memory and the histone code. Cell, 111, 285-291.
40. Fahrner, J.A. and Baylin, S.B. (2003) Heterochromatin: Stable and unstable invasions at home and abroad. Genes Dev., 17, 1805-1812.
41. Robertson, K.D., Ait-Si-Ali, S., Yokochi, T., Wade, P.A., Jones, P.L. and Wolffe, A.P. (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat. Genet., 25, 338-342.
42. Fuks, F., Burgers, W.A., Godin, N., Kasai, M. and Kouzarides, T. (2001) Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J., 20, 2536-2544.
43. Fuks, F., Hurd, P.J., Deplus, R. and Kouzarides, T. (2003) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res., 31, 2305-2312.
44. Fuks, F., Hurd, P.J., Wolf, D., Nan, X., Bird, A.P. and Kouzarides, T. (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J. Biol. Chem., 278, 4035-4040.
45. Stimson, K.M. and Vertino, P.M. (2002) Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture. J. Biol. Chem. 277, 4951-4958.
46. Stirzaker, C., Song, J.Z., Davidson, B. and Clark, S.J. (2004) Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells. Cancer Res., 64, 3871-3877.
47. Fraga, M.F., Herranz, M., Espada, J., Ballestar, E., Paz, M.F., Ropero, S., Erkek, E., Bozdogan, O., Peinado, H., Niveleau, A. et al. (2004) A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res., 64, 5527-5534.
48. Sparmann, A. and van Lohuizen, M. (2006) Polycomb silencers control cell fate, development and cancer. Nat. Rev. Cancer, 6, 846-856.
49. Matarazzo, M.R., De Bonis, M.L., Strazzullo, M., Cerase, A., Ferraro, M., Vastarelli, P., Ballestar, E., Esteller, M., Kudo, S. and D'Esposito, M. (2007) Multiple binding of methyl-CpG and polycomb proteins in long-term gene silencing events. J. Cell Physiol., 210, 711-719.
50. Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y. and Fuks, F. (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871-874.
51. Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B.E., Bergman, Y., Simon, I. and Cedar, H. (2006) Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet., doi:10.1038/ng1950.
52. Widschwendter, M., Fiegl, H., Egle, D., Mueller-Holzner, E., Spizzo, G., Marth, C., Weisenberger, D.J., Campan, M., Young, J., Jacobs, I. and Laird, P.W. (2006) Epigenetic stem cell signature in cancer. Nat. Genet., doi:10.1038/ng1941.
53. de Bustros, A., Nelkin, B.D., Silverman, A., Ehrlich, G., Poiesz, B. and Baylin, S.B. (1988) The short arm of chromosome 11 is a 'hot spot' for hypermethylation in human neoplasia. Proc. Natl. Acad. Sci. USA, 85, 5693-5697.
54. Esteller, M. (2005) Aberrant DNA methylation as a cancer-inducing mechanism. Annu. Rev. Pharmacol. Toxicol., 45, 629-656.
55. Costello, J.F., Fruhwald, M.C., Smiraglia, D.J., Rush, L.J., Robertson, G.P., Gao, X., Wright, F.A., Feramisco, J.D., Peltomaki, P., Lang, J.C., Schuller, D.E., Yu, L., Bloomfield, C.D., Caligiuri, M.A., Yates, A., Nishikawa, R., Su Huang, H., Petrelli, N.J., Zhang, X., O'Dorisio, M.S., Held, W.A., Cavenee, W.K. and Plass, C. (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat. Genet., 24, 132-138.
56. Esteller, M., Corn, P.G., Baylin, S.B. and Herman, J.G. (2001) A gene hypermethylation profile of human cancer. Cancer Res., 61, 3225-3229.
57. Esteller, M., Fraga, M.F., Guo, M., Garcia-Foncillas, J., Hedenfalk, I., Godwin, A.K., Trojan, J., Vaurs-Barriere, C., Bignon, Y.J., Ramus, S., Benitez, J., Caldes, T., Akiyama, Y., Yuasa, Y., Launonen, V., Canal, M.J., Rodriguez, R., Capella, G., Peinado, M.A., Borg, A., Aaltonen, L.A., Ponder, B.A., Baylin, S.B. and Herman, J.G. (2001) DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum. Mol. Genet., 10, 3001-3007.
58. Smiraglia, D.J., Rush, L.J., Fruhwald, M.C., Dai, Z., Held, W.A., Costello, J.F., Lang, J.C., Eng, C., Li, B., Wright, F.A., Caligiuri, M.A. and Plass, C. (2001) Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum. Mol. Genet. 10, 1413-1419.
59. Paz, M.F., Fraga, M.F., Avila, S., Guo, M., Pollan, M., Herman, J.G. and Esteller, M. (2003) A systematic profile of DNA methylation in human cancer cell lines. Cancer Res., 63, 1114-1121.
60. Esteller, M. and Herman, J.G. (2004) Generating mutations but providing chemosensitivity: The role of O6-methylguanine DNA methyltransferase in human cancer. Oncogene, 23, 1-8.
61. Hedenfalk, I., Duggan, D., Chen, Y., Radmacher, M., Bittner, M., Simon, R., Meltzer, P., Gusterson, B., Esteller, M., Kallioniemi, O.P., Wilfond, B., Borg, A., Trent, J., Raffeld, M., Yakhini, Z., Ben-Dor, A., Dougherty, E,. Kononen, J., Bubendorf, L., Fehrle, W., Pittaluga, S., Gruvberger, S., Loman, N., Johannsson, O., Olsson, H. and Sauter, G. (2001) Gene-expression profiles in hereditary breast cancer. N. Engl. J. Med., 344, 539-548.
62. Chen, W.Y. (2003) Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors. Nat. Genet., 33 197-202.
63. Ropero, S., Setien, F., Espada, J., Fraga, M.F., Herranz, M., Asp, J., Benassi, M.S., Franchi, A., Patino, A., Ward, L.S., Bovee, J., Cigudosa, J.C., Wim, W. and Esteller, M. (2004) Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells. Hum. Mol. Genet., 13, 2753-2765.
64. Agrelo, R., Cheng, W.H., Setien, F., Ropero, S., Espada, J., Fraga, M.F., Herranz, M., Paz, M.F., Sanchez-Cespedes, M., Artiga, M.J., Guerrero, D., Castells, A., von Kobbe, C., Bohr, V.A. and Esteller, M. (2006) Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc. Natl. Acad. Sci. USA, 103, 8822-8827.
65. Keshet, I., Schlesinger, Y., Farkash, S., Rand, E., Hecht, M., Segal, E., Pikarski, E., Young, R.A., Niveleau, A., Cedar, H. and Simon, I. (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat. Genet., 38, 149-153.
66. Feltus, F.A., Lee, E.K., Costello, J.F., Plass, C. and Vertino, P.M. (2006) DNA motifs associated with aberrant CpG island methylation. Genomics, 87, 572-579.
67. Shu, J., Jelinek, J., Chang, H., Shen, L., Qin, T., Chung, W., Oki, Y. and Issa, J.P. (2006) Silencing of bidirectional promoters by DNA methylation in tumorigenesis. Cancer Res., 66, 5077-5084.
68. Ying, J., Li, H., Cui, Y., Wong, A.H., Langford, C. and Tao, Q. (2006) Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/ FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter. Leukemia, 20, 1173-1175.
69. Graff, J.R., Herman, J.G., Myohanen, S., Baylin, S.B. and Vertino, P.M. (1997) Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation. J. Biol. Chem., 272, 22322-22329.
70. Frigola, J., Song, J., Stirzaker, C., Hinshelwood, R.A., Peinado, M.A. and Clark, S.J. (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat. Genet., 38, 540-549.
71. Bernstein, B.E., Mikkelsen, T.S., Xie, X., Kamal, M., Huebert, D.J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., Jaenisch, R., Wagschal, A., Feil, R., Schreiber, S.L. and Lander, E.S. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125, 315-326.
72. Azuara, V., Perry, P., Sauer, S., Spivakov, M., Jorgensen, H.F., John, R.M., Gouti, M., Casanova, M., Warnes, G., Merkenschlager, M., Fisher, A.G. (2006) Chromatin signatures of pluripotent cell lines. Nat. Cell. Biol., 8, 532-538.
73. Feinberg, A.P., Ohlsson, R. and Henikoff, S. The epigenetic progenitor origin of human cancer. Nat. Rev. Genet., 7, 21-33.
74. Crawford, Y.G., Gauthier, M.L., Joubel, A., Mantei, K., Kozakiewicz, K., Afshari, C.A. and Tlsty, T.D. (2004) Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell, 5, 263-273.
75. Weber, M., Davies, J.J., Wittig, D., Oakeley, E.J., Haase, M., Lam, W.L., Schubeler, D. (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat. Genet., 37, 853-862.
76. Suzuki, H., Gabrielson, E., Chen, W., Anbazhagan, R., van Engeland, M., Weijenberg, M.P., Herman, J.G., Baylin, S.B. (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat. Genet., 31, 141-149.
77. Yamashita, K., Upadhyay, S., Osada, M., Hoque, M.O., Xiao, Y., Mori, M., Sato, F., Meltzer, S.J. and Sidransky, D. (2002) Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell, 2, 485-495.
78. Esteller, M. (2000) Epigenetic lesions causing genetic lesions in human cancer: Promoter hypermethylation of DNA repair genes. Eur. J. Cancer 36, 2294-2300.
79. Esteller, M., Hamilton, S.R., Burger, P.C., Baylin, S.B. and Herman, J.G. (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res., 59, 793-797.
80. Hisama, F.M., Bohr, V.A. and Oshima, J. (2006) WRN's tenth anniversary. Sci. Aging Knowledge Environ., 28, pe18.
81. Di Croce, L., Raker, V.A., Corsaro, M., Fazi, F., Fanelli, M., Faretta, M., Fuks, F., Lo Coco, F., Kouzarides, T., Nervi, C., Minucci, S. and Pelicci, P.G. (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science, 295, 1079-1082.
82. Esteller, M., Fraga, M.F., Paz, M.F., Campo, E., Colomer, D., Novo, F.J., Calasanz, M.J., Galm, O., Guo, M., Benitez, J. and Herman, J.G. (2002) Cancer epigenetics and methylation. Science, 297, 1807-1808.
83. Brenner, C., Deplus, R., Didelot, C., Loriot, A., Vire, E., De Smet, C., Gutierrez, A., Danovi, D., Bernard, D., Boon, T., Pelicci, P.G., Amati, B., Kouzarides, T., de Launoit, Y., Di Croce, L. and Fuks, F. (2005) Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J., 24, 336-346.
84. Weisenberger, D.J., Siegmund, K.D., Campan, M., Young, J., Long, T.I., Faasse, M.A., Kang, G.H., Widschwendter, M., Weener, D., Buchanan, D., Koh, H., Simms, L., Barker, M., Leggett, B., Levine, J., Kim, M., French, A.J., Thibodeau, S.N., Jass, J., Haile, R. and Laird, P.W. (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat. Genet., 38, 787-793.
85. Ershler, W.B. and Longo, D.L. (1997) Aging and cancer: Issues of basic and clinical science. J. Natl. Cancer Inst., 89, 1489-1497.
86. Agrelo, R., Setien, F., Espada, J., Artiga, M.J., Rodriguez, M., Perez-Rosado, A., Sanchez-Aguilera, A., Fraga, M.F., Piris, M.A. and Esteller, M. (2005) Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B-cell lymphoma. J. Clin. Oncol., 23, 3940-3947.
87. Hutchinson, C.J. and Worman, H.J. (2004) A-type lamins: Guardians of the soma? Nat. Cell. Biol., 6, 1062-1067.
88. Broers, J.L., Ramaekers, F.C., Bonne, G., Yaou, R.B. and Hutchison, C.J. (2006) Nuclear lamins: Laminopathies and their role in premature ageing. Physiol. Rev., 86, 967-1008.
89. Stadelmann, B., Khandjian, E., Hirt, A., Luthy, A., Weil, R. and Wagner, H.P. (1990) Repression of nuclear lamin A and C gene expression in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells. Leuk. Res., 14, 815-821.
90. Epstein, C.J., Martin, G.M., Schultz, A.L. and Motulsky, A.G. (1966) Werner's syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore), 45, 177-221.
91. Opresko, P.L., Cheng, W.H., von Kobbe, C., Harrigan, J.A. and Bohr, V.A. (2003) Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis, 24, 791-802.
92. Hickson, I.D. (2003) RecQ helicases: Caretakers of the genome. Nat. Rev. Cancer, 3, 169-178.
93. He, L. and Hannon, G.J. (2004) MicroRNAs: Small RNAs with a big role in gene regulation. Nat. Rev. Genet., 5, 522-531.
94. Miska, E.A. (2005) How microRNAs control cell division, differentiation and death. Curr. Opin. Genet., 5, 563-568.
95. Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B.L., Mak, R.H., Ferrando, A.A., Downing, J.R., Jacks, T., Horvitz, H.R., Golub, T.R. (2005) MicroRNA expression profiles classify human cancers. Nature, 435, 834-838(Baltimore).
96. Calin, G.A. and Croce, C.M. (2006) MicroRNA signatures in human cancers. Nat. Rev. Cancer, 6, 857-866.
97. Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D. and Slack, F.J. (2005) RAS is regulated by the let-7 microRNA family. Cell, 120 635-647.
98. Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C.G., Kipps, T.J., Negrini, M. and Croce, C.M. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci., 102, 13944-13949.
99. Thomson, J.M., Newman, M., Parker, J.S., Morin-Kensicki, E.M., Wright, T. and Hammond, S.M. (2006) Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev., 20, 2202-2207.