Advertisement

Epigenetics of Colorectal Cancer

  • F. Javier Carmona
  • Manel EstellerEmail author
Chapter
Part of the Cancer Metastasis - Biology and Treatment book series (CMBT, volume 14)

Abstract

Epigenetic research is increasingly gaining prominence as it provides new insights in explaining human diseases, as well as new diagnostic and prognostic tools. Colorectal cancer is a prime model for cancer epigenetics, as aberrant DNA methylation processes characterize all stages of the disease. This chapter recapitulates the contribution of epigenetics to colorectal cancer research, emphasizing its connection to human cancer metastasis.

Key words

Epigenetics DNA methylation Histones MicroRNAs Metastasis 

Abbreviations and Acronyms

APC

Adenomatous polyposis coli

BAGE

B-melanoma antigens

BRCA1

Breast cancer susceptibility gene 1

CDKN2A

Cyclin D kinase N2A

ChIP

Chromatin Immunoprecipitation

CRC

Colorectal cancer

CpG

Cytosine-phosphate-guanine

DIRAS

GTP-binding RAS-like 3

DNMTs

DNA methyltransferases

5mC

5-methylcytosine

HDACs

Histone deacetylases

HERV

Human endogenous retrovirus

IGF

Insulin like growth factor

LINE-1

Long interspersed nuclear element 1

LOI

Loss of imprinting

LTR

Long terminal repeat

MAGE

Melanoma-associated antigens

MeDIP

Methylated DNA immunoprecipitation

MEST

Mouse mesoderm-specific transcript

miRNA

microRNA

MeDIP

Methylated DNA immunoprecipitation

MEST

Mouse mesoderm-specific transcript

miRNA

microRNA

NF-kB

Nuclear factor kappa light chain enhancer of activated B cells

SAHA

Suberoylanilide hydroxamic acid

TARBP2

TAR RNA-binding protein 2

TPEF

Transmembrane protein containing epidermal growth factor and follistatin domain

TSA

Trichostatin

VHL

Von Hippel-Lindau

References

  1. Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP (1998). Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 58: 5489–94.PubMedGoogle Scholar
  2. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S et al. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27: 2128–36.PubMedGoogle Scholar
  3. Bariol C, Suter C, Cheong K, Ku SL, Meagher A, Hawkins N et al. (2003). The relationship between hypomethylation and CpG island methylation in colorectal neoplasia. Am J Pathol 162: 1361–71.PubMedGoogle Scholar
  4. Baylin SB (2005). DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol 2 (Suppl 1): S4–S11.PubMedGoogle Scholar
  5. Bender CM, Pao MM, Jones PA (1998). Inhibition of DNA methylation by 5-aza-2-deoxycytidine suppresses the growth of human tumor cell lines. Cancer Res 58: 95–101.PubMedGoogle Scholar
  6. Berger SL (2007). The complex language of chromatin regulation during transcription. Nature 447: 407–12.PubMedGoogle Scholar
  7. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008). Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27: 5643–47.PubMedGoogle Scholar
  8. Bibikova M, Lin Z, Zhou L, Chudin E, Garcia EW, Wu B et al. (2006). High-throughput DNA methylation profiling using universal bead arrays. Genome Res 16: 383–93.PubMedGoogle Scholar
  9. Bird A (2002). DNA methylation patterns and epigenetic memory. Genes Dev 16: 6–21.PubMedGoogle Scholar
  10. Bolden JE, Peart MJ, Johnstone RW (2006). Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5: 769–84.PubMedGoogle Scholar
  11. Bordonaro M, Mariadason JM, Aslam F, Heerdt BG, Augenlicht LH (1999). Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin. Cell Growth Differ 10: 713–20.PubMedGoogle Scholar
  12. Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, Cigudosa JC et al. (2008). Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 13: 496–506.PubMedGoogle Scholar
  13. Caldwell GM, Jones C, Gensberg K, Jan S, Hardy RG, Byrd P et al. (2004). The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer Res 64: 883–88.PubMedGoogle Scholar
  14. Calvanese V, Horrillo A, Hmadcha A, Suarez-Alvarez B, Fernandez AF, Lara E et al. (2008). Cancer genes hypermethylated in human embryonic stem cells. PLoS One 3: e3294.PubMedGoogle Scholar
  15. 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: 103–7.PubMedGoogle Scholar
  16. Casau AE, Vaughan JE, Lozano G, Levine AJ (1999). Germ cell expression of an isolated human endogenous retroviral long terminal repeat of the HERV-K/HTDV family in transgenic mice. J Virol 73: 9976–83.PubMedGoogle Scholar
  17. Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A (2002a). CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160: 1823–30.PubMedGoogle Scholar
  18. Chan AO, Issa JP, Morris JS, Hamilton SR, Rashid A (2002b). Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol 160: 529–36.PubMedGoogle Scholar
  19. Cho YG, Kim CJ, Nam SW, Yoon SH, Lee SH, Yoo NJ et al. (2005). Overexpression of S100A4 is closely associated with progression of colorectal cancer. World J Gastroenterol 11: 4852–56.PubMedGoogle Scholar
  20. Cho CY, Wang JH, Chang HC, Chang CK, Hung WC (2007). Epigenetic inactivation of the metastasis suppressor RECK enhances invasion of human colon cancer cells. J Cell Physiol 213: 65–69.PubMedGoogle Scholar
  21. Christofori G, Naik P, Hanahan D (1995). Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis. Nat Genet 10: 196–201.PubMedGoogle Scholar
  22. Corn PG, Summers MK, Fogt F, Virmani AK, Gazdar AF, Halazonetis TD et al. (2003). Frequent hypermethylation of the 5 CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer. Carcinogenesis 24: 47–51.PubMedGoogle Scholar
  23. Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X et al. (2000). Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24: 132–38.PubMedGoogle Scholar
  24. Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S et al. (2003). Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299: 1753–55.PubMedGoogle Scholar
  25. Cui H, Horon IL, Ohlsson R, Hamilton SR, Feinberg AP (1998). Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat Med 4: 1276–80.PubMedGoogle Scholar
  26. Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP (2002). Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62: 6442–46.PubMedGoogle Scholar
  27. De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T (1996). The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 93: 7149–53.PubMedGoogle Scholar
  28. Ebert MP, Mooney SH, Tonnes-Priddy L, Lograsso J, Hoffmann J, Chen J et al. (2005). Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal cancers. Neoplasia 7: 771–78.PubMedGoogle Scholar
  29. Ehrlich M (2002). DNA methylation in cancer: too much, but also too little. Oncogene 21: 5400–13.PubMedGoogle Scholar
  30. Esteller M (2006). CpG island methylation and histone modifications: biology and clinical significance. Ernst Schering Res Found Workshop 57: 115–26.PubMedGoogle Scholar
  31. Esteller M (2007a). Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8: 286–98.PubMedGoogle Scholar
  32. Esteller M (2007b). Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 16(Spec No 1): R50–R59.PubMedGoogle Scholar
  33. Esteller M (2008). Epigenetics in cancer. N Engl J Med 358: 1148–59.PubMedGoogle Scholar
  34. Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA et al. (2000a). Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene 19: 164–68.PubMedGoogle Scholar
  35. Esteller M, Corn PG, Baylin SB, Herman JG (2001). A gene hypermethylation profile of human cancer. Cancer Res 61: 3225–29.PubMedGoogle Scholar
  36. Esteller M, Guo M, Moreno V, Peinado MA, Capella G, Galm O et al. (2002). Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer. Cancer Res 62: 5902–5.PubMedGoogle Scholar
  37. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E et al. (2000b). Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92: 564–69.PubMedGoogle Scholar
  38. Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA et al. (2000c). Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 60: 4366–71.PubMedGoogle Scholar
  39. Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB et al. (2000d). Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 mutational status. Cancer Res 60: 129–33.PubMedGoogle Scholar
  40. Feinberg AP, Ohlsson R, Henikoff S (2006). The epigenetic progenitor origin of human cancer. Nat Rev Genet 7: 21–33.PubMedGoogle Scholar
  41. Feinberg AP, Vogelstein B (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301: 89–92.PubMedGoogle Scholar
  42. Feltus FA, Lee EK, Costello JF, Plass C, Vertino PM (2006). DNA motifs associated with aberrant CpG island methylation. Genomics 87: 572–79.PubMedGoogle Scholar
  43. Fisher AG (2002). Cellular identity and lineage choice. Nat Rev Immunol 2: 977–82.PubMedGoogle Scholar
  44. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML et al. (2005a). Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102: 10604–9.PubMedGoogle Scholar
  45. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G et al. (2005b). Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37: 391–400.PubMedGoogle Scholar
  46. Frigola J, Ribas M, Risques RA, Peinado MA (2002). Methylome profiling of cancer cells by amplification of inter-methylated sites (AIMS). Nucl Acids Res 30: e28.PubMedGoogle Scholar
  47. Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW et al. (1983). The 5-methylcytosine content of DNA from human tumors. Nucl Acids Res 11: 6883–94.PubMedGoogle Scholar
  48. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW et al. (2003). Induction of tumors in mice by genomic hypomethylation. Science 300: 489–92.PubMedGoogle Scholar
  49. Giovannucci E (2002). Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 132: 2350S–2355S.PubMedGoogle Scholar
  50. Gonzalez-Sancho JM, Aguilera O, Garcia JM, Pendas-Franco N, Pena C, Cal S et al. (2005). The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. Oncogene 24: 1098–103.PubMedGoogle Scholar
  51. Gonzalez-Zulueta M, Bender CM, Yang AS, Nguyen T, Beart RW, Van Tornout JM et al. (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: 4531–35.PubMedGoogle Scholar
  52. Gore SD, Hermes-DeSantis ER (2008). Future directions in myelodysplastic syndrome: newer agents and the role of combination approaches. Cancer Control 15(Suppl): 40–49.PubMedGoogle Scholar
  53. Grady WM (2005). Epigenetic events in the colorectum and in colon cancer. Biochem Soc Trans 33: 684–88.PubMedGoogle Scholar
  54. Grady WM, Parkin RK, Mitchell PS, Lee JH, Kim YH, Tsuchiya KD et al. (2008). Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene 27: 3880–88.PubMedGoogle Scholar
  55. 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: 155–58.PubMedGoogle Scholar
  56. Grunau C, Brun ME, Rivals I, Selves J, Hindermann W, Favre-Mercuret M et al. (2008). BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection. Cancer Epidemiol Biomarkers Prev 17: 1374–79.PubMedGoogle Scholar
  57. Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell 100: 57–70.PubMedGoogle Scholar
  58. Hawkins NJ, Ward RL (2001). Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst 93: 1307–13.PubMedGoogle Scholar
  59. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S et al. (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65: 9628–32.PubMedGoogle Scholar
  60. He L, Hannon GJ (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5: 522–31.PubMedGoogle Scholar
  61. Herman JG, Baylin SB (2003). Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349: 2042–54.PubMedGoogle Scholar
  62. Herman JG, Jen J, Merlo A, Baylin SB (1996). Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res 56: 722–27.PubMedGoogle Scholar
  63. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S et al. (1994). Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91: 9700–4.PubMedGoogle Scholar
  64. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP et al. (1998). Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95: 6870–75.PubMedGoogle Scholar
  65. Hernandez-Blazquez FJ, Habib M, Dumollard JM, Barthelemy C, Benchaib M, de Capoa A et al. (2000). Evaluation of global DNA hypomethylation in human colon cancer tissues by immunohistochemistry and image analysis. Gut 47: 689–93.PubMedGoogle Scholar
  66. Hibi K, Kodera Y, Ito K, Akiyama S, Nakao A (2005). Aberrant methylation of HLTF, SOCS-1, and CDH13 genes is shown in colorectal cancers without lymph node metastasis. Dis Colon Rectum 48: 1282–86.PubMedGoogle Scholar
  67. Hiltunen MO, Koistinaho J, Alhonen L, Myohanen S, Marin S, Kosma VM et al. (1997). Hypermethylation of the WT1 and calcitonin gene promoter regions at chromosome 11p in human colorectal cancer. Br J Cancer 76: 1124–30.PubMedGoogle Scholar
  68. Huang TH, Perry MR, Laux DE (1999). Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet 8: 459–70.PubMedGoogle Scholar
  69. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P et al. (2009). The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41: 178–86.PubMedGoogle Scholar
  70. Issa JP, Kantarjian H (2005). Azacitidine. Nat Rev Drug Discov (Suppl): S.Google Scholar
  71. 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: 536–40.PubMedGoogle Scholar
  72. Jacinto FV, Ballestar E, Ropero S, Esteller M (2007). Discovery of epigenetically silenced genes by methylated DNA immunoprecipitation in colon cancer cells. Cancer Res 67: 11481–86.PubMedGoogle Scholar
  73. Jones PA, Baylin SB (2002). The fundamental role of epigenetic events in cancer. Nat Rev Genet 3: 415–28.PubMedGoogle Scholar
  74. Kang MJ, Park BJ, Byun DS, Park JI, Kim HJ, Park JH et al. (2000). Loss of imprinting and elevated expression of wild-type p73 in human gastric adenocarcinoma. Clin Cancer Res 6: 1767–71.PubMedGoogle Scholar
  75. Kim YI (2004). Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev 13: 511–19.PubMedGoogle Scholar
  76. Kim YI (2005). Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 135: 2703–9.PubMedGoogle Scholar
  77. Kim KH, Choi JS, Kim IJ, Ku JL, Park JG (2006). Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues. World J Gastroenterol 12: 5651–57.PubMedGoogle Scholar
  78. Kim H, Kim YH, Kim SE, Kim NG, Noh SH, Kim H (2003). Concerted promoter hypermethylation of hMLH1, p16INK4A, and E-cadherin in gastric carcinomas with microsatellite instability. J Pathol 200: 23–31.PubMedGoogle Scholar
  79. Kim HC, Roh SA, Ga IH, Kim JS, Yu CS, Kim JC (2005). CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer. J Gastroenterol Hepatol 20: 1920–26.PubMedGoogle Scholar
  80. Kondo Y, Issa JP (2004). Epigenetic changes in colorectal cancer. Cancer Metastasis Rev 23: 29–39.PubMedGoogle Scholar
  81. Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS et al. (2008). MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol 28: 6773–84.PubMedGoogle Scholar
  82. Kopelovich L, Crowell JA, Fay JR (2003). The epigenome as a target for cancer chemoprevention. J Natl Cancer Inst 95: 1747–57.PubMedGoogle Scholar
  83. Kouzarides T (2007). Chromatin modifications and their function. Cell 128: 693–705.PubMedGoogle Scholar
  84. Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J (2008). Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res 68: 2094–105.PubMedGoogle Scholar
  85. Ku JL, Kang SB, Shin YK, Kang HC, Hong SH, Kim IJ et al. (2004). Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines. Oncogene 23: 6736–42.PubMedGoogle Scholar
  86. Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, Li E et al. (1995). Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81: 197–205.PubMedGoogle Scholar
  87. Lantry LE, Zhang Z, Crist KA, Wang Y, Kelloff GJ, Lubet RA et al. (1999). 5-Aza-2-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model. Carcinogenesis 20: 343–46.PubMedGoogle Scholar
  88. Lee MP, DeBaun MR, Mitsuya K, Galonek HL, Brandenburg S, Oshimura M et al. (1999). Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. Proc Natl Acad Sci USA 96: 5203–8.PubMedGoogle Scholar
  89. Lee S, Hwang KS, Lee HJ, Kim JS, Kang GH (2004). Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia. Lab Invest 84: 884–93.PubMedGoogle Scholar
  90. Lee M, Sup Han W, Kyoung Kim O, Hee Sung S, Sun Cho M, Lee SN et al. (2006). Prognostic value of p16INK4a and p14ARF gene hypermethylation in human colon cancer. Pathol Res Pract 202: 415–24.PubMedGoogle Scholar
  91. Lehmann U, Hasemeier B, Christgen M, Muller M, Romermann D, Langer F et al. (2008). Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol 214: 17–24.PubMedGoogle Scholar
  92. Leib-Mosch C, Haltmeier M, Werner T, Geigl EM, Brack-Werner R, Francke U et al. (1993). Genomic distribution and transcription of solitary HERV-K LTRs. Genomics 18: 261–69.PubMedGoogle Scholar
  93. Lengauer C, Kinzler KW, Vogelstein B (1997). DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci USA 94: 2545–50.PubMedGoogle Scholar
  94. Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L et al. (2003). SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci USA 100: 8412–17.PubMedGoogle Scholar
  95. Lind GE, Ahlquist T, Kolberg M, Berg M, Eknaes M, Alonso MA et al. (2008). Hypermethylated MAL gene – a silent marker of early colon tumorigenesis. J Transl Med 6: 13.PubMedGoogle Scholar
  96. Loh K, Chia JA, Greco S, Cozzi SJ, Buttenshaw RL, Bond CE et al. (2008). Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development. Genes Chromosomes Cancer 47: 449–60.PubMedGoogle Scholar
  97. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. (2005). MicroRNA expression profiles classify human cancers. Nature 435: 834–38.PubMedGoogle Scholar
  98. Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D et al. (2008). A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 105: 13556–61.PubMedGoogle Scholar
  99. Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setien F et al. (2007). Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 67: 1424–29.PubMedGoogle Scholar
  100. Ma L, Teruya-Feldstein J, Weinberg RA (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449: 682–88.PubMedGoogle Scholar
  101. Malik K, Salpekar A, Hancock A, Moorwood K, Jackson S, Charles A et al. (2000). Identification of differential methylation of the WT1 antisense regulatory region and relaxation of imprinting in Wilms’ tumor. Cancer Res 60: 2356–60.PubMedGoogle Scholar
  102. Mariadason JM (2008). HDACs and HDAC inhibitors in colon cancer. Epigenetics 3: 28–37.PubMedGoogle Scholar
  103. Mariadason JM, Corner GA, Augenlicht LH (2000). Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Cancer Res 60: 4561–72.PubMedGoogle Scholar
  104. Martin C, Zhang Y (2005). The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6: 838–49.PubMedGoogle Scholar
  105. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA et al. (2009). A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 41: 365–70.PubMedGoogle Scholar
  106. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC et al. (1995). 5 CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1: 686–92.PubMedGoogle Scholar
  107. Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW et al. (1992). Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52: 643–45.PubMedGoogle Scholar
  108. Mizukami H, Shirahata A, Goto T, Sakata M, Saito M, Ishibashi K et al. (2008). PGP9.5 methylation as a marker for metastatic colorectal cancer. Anticancer Res 28: 2697–700.PubMedGoogle Scholar
  109. Mori Y, Cai K, Cheng Y, Wang S, Paun B, Hamilton JP et al. (2006). A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer. Gastroenterology 131: 797–808.PubMedGoogle Scholar
  110. Mutskov V, Felsenfeld G (2004). Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9. EMBO J 23: 138–49.PubMedGoogle Scholar
  111. Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La Chapelle A (2001). Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci USA 98: 591–96.PubMedGoogle Scholar
  112. 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: 471–79.PubMedGoogle Scholar
  113. Narayan A, Ji W, Zhang XY, Marrogi A, Graff JR, Baylin SB et al. (1998). Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int J Cancer 77: 833–38.PubMedGoogle Scholar
  114. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA et al. (1993). Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 362: 749–51.PubMedGoogle Scholar
  115. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES et al. (2008). A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst 100: 1734–38.PubMedGoogle Scholar
  116. Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L et al. (2007). A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 39: 237–42.PubMedGoogle Scholar
  117. Ohtani-Fujita N, Fujita T, Aoike A, Osifchin NE, Robbins PD, Sakai T (1993). CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene 8: 1063–67.PubMedGoogle Scholar
  118. Otterson GA, Khleif SN, Chen W, Coxon AB, Kaye FJ (1995). CDKN2 gene silencing in lung cancer by DNA hypermethylation and kinetics of p16INK4 protein induction by 5-aza 2deoxycytidine. Oncogene 11: 1211–16.PubMedGoogle Scholar
  119. Pakneshan P, Szyf M, Rabbani SA (2005). Methylation and inhibition of expression of uPA by the RAS oncogene: divergence of growth control and invasion in breast cancer cells. Carcinogenesis 26: 557–64.PubMedGoogle Scholar
  120. Paz MF, Avila S, Fraga MF, Pollan M, Capella G, Peinado MA et al. (2002). Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors. Cancer Res 62: 4519–24.PubMedGoogle Scholar
  121. Paz MF, Wei S, Cigudosa JC, Rodriguez-Perales S, Peinado MA, Huang TH et al. (2003). Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases. Hum Mol Genet 12: 2209–19.PubMedGoogle Scholar
  122. Pedersen IS, Dervan PA, Broderick D, Harrison M, Miller N, Delany E et al. (1999). Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. Cancer Res 59: 5449–51.PubMedGoogle Scholar
  123. Peng Z, Wei D, Wang L, Tang H, Zhang J, Le X et al. (2006). RUNX3 inhibits the expression of vascular endothelial growth factor and reduces the angiogenesis, growth, and metastasis of human gastric cancer. Clin Cancer Res 12: 6386–94.PubMedGoogle Scholar
  124. Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993). Relaxation of imprinted genes in human cancer. Nature 362: 747–49.PubMedGoogle Scholar
  125. Ramirez N, Bandres E, Navarro A, Pons A, Jansa S, Moreno I et al. (2008). Epigenetic events in normal colonic mucosa surrounding colorectal cancer lesions. Eur J Cancer 44: 2689–95.PubMedGoogle Scholar
  126. Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR (2001). CpG island methylation in colorectal adenomas. Am J Pathol 159: 1129–35.PubMedGoogle Scholar
  127. Rothberg PG, Ponnuru S, Baker D, Bradley JF, Freeman AI, Cibis GW et al. (1997). A deletion polymorphism due to Alu-Alu recombination in intron 2 of the retinoblastoma gene: association with human gliomas. Mol Carcinog 19: 69–73.PubMedGoogle Scholar
  128. Sabbioni S, Miotto E, Veronese A, Sattin E, Gramantieri L, Bolondi L et al. (2003). Multigene methylation analysis of gastrointestinal tumors: TPEF emerges as a frequent tumor-specific aberrantly methylated marker that can be detected in peripheral blood. Mol Diagn 7: 201–7.PubMedGoogle Scholar
  129. Saito Y, Jones PA (2006). Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 5: 2220–22.PubMedGoogle Scholar
  130. Santini V, Kantarjian HM, Issa JP (2001). Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med 134: 573–86.PubMedGoogle Scholar
  131. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J et al. (2007). Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet 39: 232–36.PubMedGoogle Scholar
  132. Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M et al. (2005). Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435: 1262–66.PubMedGoogle Scholar
  133. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ et al. (2008). MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci USA 105: 5874–78.PubMedGoogle Scholar
  134. Sharrard RM, Royds JA, Rogers S, Shorthouse AJ (1992). Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br J Cancer 65: 667–72.PubMedGoogle Scholar
  135. Shilatifard A (2006). Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75: 243–69.PubMedGoogle Scholar
  136. Spurling CC, Suhl JA, Boucher N, Nelson CE, Rosenberg DW, Giardina C (2008). The short chain fatty acid butyrate induces promoter demethylation and reactivation of RARbeta2 in colon cancer cells. Nutr Cancer 60: 692–702.PubMedGoogle Scholar
  137. Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP et al. (2002). A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31: 141–49.PubMedGoogle Scholar
  138. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD et al. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451: 147–52.PubMedGoogle Scholar
  139. Toyota M, Ho C, Ahuja N, Jair KW, Li Q, Ohe-Toyota M et al. (1999). Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 59: 2307–12.PubMedGoogle Scholar
  140. Toyota M, Sasaki Y, Satoh A, Ogi K, Kikuchi T, Suzuki H et al. (2003). Epigenetic inactivation of CHFR in human tumors. Proc Natl Acad Sci USA 100: 7818–23.PubMedGoogle Scholar
  141. van Engeland M, Weijenberg MP, Roemen GM, Brink M, de Bruine AP, Goldbohm RA et al. (2003). Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. Cancer Res 63: 3133–37.PubMedGoogle Scholar
  142. Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R et al. (2006). A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124: 1169–81.PubMedGoogle Scholar
  143. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL et al. (2005). Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37: 853–62.PubMedGoogle Scholar
  144. Weber B, Stresemann C, Brueckner B, Lyko F (2007). Methylation of human microRNA genes in normal and neoplastic cells. Cell Cycle 6: 1001–5.PubMedGoogle Scholar
  145. Wendt MK, Johanesen PA, Kang-Decker N, Binion DG, Shah V, Dwinell MB (2006). Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis. Oncogene 25: 4986–97.PubMedGoogle Scholar
  146. Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C et al. (2007). Epigenetic stem cell signature in cancer. Nat Genet 39: 157–58.PubMedGoogle Scholar
  147. Wolffe AP, Matzke MA (1999). Epigenetics: regulation through repression. Science 286: 481–86.PubMedGoogle Scholar
  148. Woodson K, Flood A, Green L, Tangrea JA, Hanson J, Cash B et al. (2004). Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women. J Natl Cancer Inst 96: 407–10.PubMedGoogle Scholar
  149. Wynter CV, Kambara T, Walsh MD, Leggett BA, Young J, Jass JR (2006). DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients. Int J Cancer 118: 907–15.PubMedGoogle Scholar
  150. Xu XL, Yu J, Zhang HY, Sun MH, Gu J, Du X et al. (2004). Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J Gastroenterol 10: 3441–54.PubMedGoogle Scholar
  151. Yamashita K, Upadhyay S, Osada M, Hoque MO, Xiao Y, Mori M et al. (2002). Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell 2: 485–95.PubMedGoogle Scholar
  152. Yoo CB, Jones PA (2006). Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5: 37–50.PubMedGoogle Scholar
  153. Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y et al. (1999). NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. Proc Natl Acad Sci USA 96: 214–19.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Cancer Epigenetics and Biology Program (PEBC)Bellvitge Institute for Biomedical Research (IDIBELL)BarcelonaSpain

Personalised recommendations