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Pathology Research International
Volume 2011, Article ID 902674, 8 pages
http://dx.doi.org/10.4061/2011/902674
Review Article

CpG Island Methylation in Colorectal Cancer: Past, Present and Future

1Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA
2Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA

Received 11 November 2010; Revised 13 January 2011; Accepted 26 January 2011

Academic Editor: Alyssa M. Krasinskas

Copyright © 2011 Karen Curtin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Bonasio, S. Tu, and D. Reinberg, “Molecular signals of epigenetic states,” Science, vol. 330, no. 6004, pp. 612–616, 2010. View at Publisher · View at Google Scholar · View at PubMed
  2. M. Esteller, “Molecular origins of cancer: epigenetics in cancer,” New England Journal of Medicine, vol. 358, no. 11, pp. 1148–1096, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. A. P. Feinberg and B. Vogelstein, “Hypomethylation distinguishes genes of some human cancers from their normal counterparts,” Nature, vol. 301, no. 5895, pp. 89–92, 1983. View at Google Scholar · View at Scopus
  4. V. Greger, E. Passarge, W. Hopping, E. Messmer, and B. Horsthemke, “Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma,” Human Genetics, vol. 83, no. 2, pp. 155–158, 1989. View at Google Scholar · View at Scopus
  5. A. Lujambio, S. Ropero, E. Ballestar et al., “Genetic unmasking of an epigenetically silenced microRNA in human cancer cells,” Cancer Research, vol. 67, no. 4, pp. 1424–1429, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. W. S. Samowitz, “The CpG island methylator phenotype in colorectal cancer,” Journal of Molecular Diagnostics, vol. 9, no. 3, pp. 281–283, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. M. Toyota, N. Ahuja, M. Ohe-Toyota, J. G. Herman, S. B. Baylin, and J. P. J. Issa, “CpG island methylator phenotype in colorectal cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 15, pp. 8681–8686, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. B. Vogelstein, E. R. Fearon, S. R. Hamilton et al., “Genetic alterations during colorectal-tumor development,” New England Journal of Medicine, vol. 319, no. 9, pp. 525–532, 1988. View at Google Scholar · View at Scopus
  9. J. P. J. Issa, L. Shen, and M. Toyota, “CIMP, at last,” Gastroenterology, vol. 129, no. 3, pp. 1121–1124, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. P. W. Laird, “Cancer epigenetics,” Human Molecular Genetics, vol. 14, no. 1, pp. R65–R76, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. W. S. Samowitz, H. Albertsen, J. Herrick et al., “Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer,” Gastroenterology, vol. 129, no. 3, pp. 837–845, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. J. R. Jass, “Colorectal cancer: a multipathway disease,” Critical Reviews in Oncogenesis, vol. 12, no. 3-4, pp. 273–287, 2006. View at Google Scholar · View at Scopus
  13. D. J. Weisenberger, K. D. Siegmund, M. Campan et al., “CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer,” Nature Genetics, vol. 38, no. 7, pp. 787–793, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. S. Ogino and A. Goel, “Molecular classification and correlates in colorectal cancer,” Journal of Molecular Diagnostics, vol. 10, no. 1, pp. 13–27, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. A. McGivern, C. V. A. Wynter, V. L. J. Whitehall et al., “Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer,” Familial Cancer, vol. 3, no. 2, pp. 101–107, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. N. Hawkins, M. Norrie, K. Cheong et al., “CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability,” Gastroenterology, vol. 122, no. 5, pp. 1376–1387, 2002. View at Google Scholar · View at Scopus
  17. M. Van Rijnsoever, F. Grieu, H. Elsaleh, D. Joseph, and B. Iacopetta, “Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands,” Gut, vol. 51, no. 6, pp. 797–802, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. M. L. Slattery, K. Curtin, R. K. Wolff et al., “A comparison of colon and rectal somatic DNA alterations,” Diseases of the Colon and Rectum, vol. 52, no. 7, pp. 1304–1311, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. L. Barault, C. Charon-Barra, V. Jooste et al., “Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases,” Cancer Research, vol. 68, no. 20, pp. 8541–8546, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. K. Nosho, N. Irahara, K. Shima et al., “Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample,” PLoS ONE, vol. 3, no. 11, article e3698, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. D. R. English, J. P. Young, J. A. Simpson et al., “Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype,” Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 7, pp. 1774–1780, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. C. P. Vaughn, A. R. Wilson, and W. S. Samowitz, “Quantitative evaluation of CpG island methylation in hyperplastic polyps,” Modern Pathology, vol. 23, no. 1, pp. 151–156, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. G. B. Baretton, F. Autschbach, and S. Baldus, “Histopathological diagnosis and differential diagnosis of colorectal serrated polys: findings of a consensus conference of the working group “Gastroenterological pathology of the German Society of Pathology”,” Pathologe, vol. 32, no. 1, pp. 76–82, 2011. View at Google Scholar
  24. E. E. Torlakovic, J. D. Gomez, D. K. Driman et al., “Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA),” American Journal of Surgical Pathology, vol. 32, no. 1, pp. 21–29, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. L. Shen, P. J. Catalano, AL. B. Benson, P. O'Dwyer, S. R. Hamilton, and J. P. J. Issa, “Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil-based chemotherapy,” Clinical Cancer Research, vol. 13, no. 20, pp. 6093–6098, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. S. Ogino, J. A. Meyerhardt, T. Kawasaki et al., “CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma,” Virchows Archiv, vol. 450, no. 5, pp. 529–537, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. A. M. Dahlin, R. Palmqvist, M. L. Henriksson et al., “The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status,” Clinical Cancer Research, vol. 16, no. 6, pp. 1845–1855, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. W. S. Samowitz, C. Sweeney, J. Herrick et al., “Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers,” Cancer Research, vol. 65, no. 14, pp. 6063–6070, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. J. H. Kim, SO. H. Shin, H. J. Kwon, N. Y. Cho, and G. H. Kang, “Prognostic implications of CpG island hypermethylator phenotype in colorectal cancers,” Virchows Archiv, vol. 455, no. 6, pp. 485–494, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. S. Ogino, K. Nosho, G. J. Kirkner et al., “CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer,” Gut, vol. 58, no. 1, pp. 90–96, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. S. J. Park, A. Rashid, J. H. Lee, S. G. Kim, S. R. Hamilton, and T. T. Wu, “Frequent CpG island methylation in serrated adenomas of the colorectum,” American Journal of Pathology, vol. 162, no. 3, pp. 815–822, 2003. View at Google Scholar · View at Scopus
  32. S. Ogino, T. Kawasaki, G. J. Kirkner, M. Loda, and C. S. Fuchs, “CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations,” Journal of Molecular Diagnostics, vol. 8, no. 5, pp. 582–588, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. L. Shen, M. Toyota, Y. Kondo et al., “Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 47, pp. 18654–18659, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. S. Ogino, M. Cantor, T. Kawasaki et al., “CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies,” Gut, vol. 55, no. 7, pp. 1000–1006, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. N. Tanaka, C. Huttenhower, K. Nosho et al., “Novel application of structural equation modeling to correlation structure analysis of CpG island methylation in colorectal cancer,” American Journal of Pathology, vol. 177, no. 6, pp. 2731–2740, 2010. View at Publisher · View at Google Scholar · View at PubMed
  36. P. W. Ang, M. Loh, N. Liem et al., “Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features,” BMC Cancer, vol. 10, article 227, 2010. View at Publisher · View at Google Scholar · View at PubMed
  37. A. Kaneda and K. Yagi, “Two groups of DNA methylation markers to classify colorectal cancer into three epigenotypes,” Cancer Science, vol. 102, no. 1, pp. 18–24, 2011. View at Publisher · View at Google Scholar · View at PubMed
  38. T. Hinoue, D. J. Weisenberger, F. Pan et al., “Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling,” PloS one, vol. 4, no. 12, p. e8357, 2009. View at Google Scholar
  39. T. Kondo and J. P. Issa, “DNA methylation profiling in cancer,” Expert Review of Proteomics, vol. 12, article e23, 2010. View at Google Scholar
  40. J. R. Jass, “Classification of colorectal cancer based on correlation of clinical, morphological and molecular features,” Histopathology, vol. 50, no. 1, pp. 113–130, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. M. Toyota, M. Ohe-Toyota, N. Ahuja, and J. P. J. Issa, “Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 2, pp. 710–715, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. S. D. Dertinger, A. E. Silverstone, and T. A. Gasiewicz, “Influence of aromatic hydrocarbon receptor-mediated events on the genotoxicity of cigarette smoke condensate,” Carcinogenesis, vol. 19, no. 11, pp. 2037–2042, 1998. View at Google Scholar · View at Scopus
  43. S. A. Belinsky, W. A. Palmisano, F. D. Gilliland et al., “Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers,” Cancer Research, vol. 62, no. 8, pp. 2370–2377, 2002. View at Google Scholar · View at Scopus
  44. S. S. Ray and H. I. Swanson, “Dioxin-induced immortalization of normal human keratinocytes and silencing of p53 and p16,” Journal of Biological Chemistry, vol. 279, no. 26, pp. 27187–27193, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. W. S. Samowitz, H. Albertsen, C. Sweeney et al., “Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer,” Journal of the National Cancer Institute, vol. 98, no. 23, pp. 1731–1738, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. K. Curtin, W. S. Samowitz, R. K. Wolff, J. Herrick, B. J. Caan, and M. L. Slattery, “Somatic alterations, metabolizing genes and smoking in rectal cancer,” International Journal of Cancer, vol. 125, no. 1, pp. 158–164, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. D. Limsui, R. A. Vierkant, L. S. Tillmans et al., “Cigarette smoking and colorectal cancer risk by molecularly defined subtypes,” Journal of the National Cancer Institute, vol. 102, no. 14, pp. 1012–1022, 2010. View at Publisher · View at Google Scholar · View at PubMed
  48. L. S. Rozek, C. M. Herron, J. K. Greenson et al., “Smoking, gender, and ethnicity predict somatic BRAF mutations in colorectal cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 3, pp. 838–843, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. M. L. Slattery, K. Curtin, K. Anderson et al., “Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors,” Journal of the National Cancer Institute, vol. 92, no. 22, pp. 1831–1836, 2000. View at Google Scholar · View at Scopus
  50. L. M. Morimoto, P. A. Newcomb, C. M. Ulrich, R. M. Bostick, C. J. Lais, and J. D. Potter, “Risk factors for hyperplastic and adenomatous polyps: evidence for malignant potential?” Cancer Epidemiology Biomarkers and Prevention, vol. 11, no. 10 I, pp. 1012–1018, 2002. View at Google Scholar · View at Scopus
  51. C. M. Ulrich, “Nutrigenetics in cancer research—folate metabolism and colorectal cancer,” Journal of Nutrition, vol. 135, no. 11, pp. 2698–2702, 2005. View at Google Scholar · View at Scopus
  52. S. J. James, S. Melnyk, M. Pogribna, I. P. Pogribny, and M. A. Caudill, “Elevation in S-Adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology,” Journal of Nutrition, vol. 132, no. 8, pp. 2361S–2366S, 2002. View at Google Scholar · View at Scopus
  53. K. Kawakami, A. Ruszkiewicz, G. Bennett, J. Moore, GO. Watanabe, and B. Iacopetta, “The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase,” Clinical Cancer Research, vol. 9, no. 16 I, pp. 5860–5865, 2003. View at Google Scholar · View at Scopus
  54. S. Ogino, T. Kawasaki, K. Nosho et al., “LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer,” International Journal of Cancer, vol. 122, no. 12, pp. 2767–2773, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. M. R. H. Estécio, V. Gharibyan, L. Shen et al., “LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability,” PLoS ONE, vol. 2, no. 5, article e399, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. M. L. Slattery, K. Curtin, C. Sweeney et al., “Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer,” International Journal of Cancer, vol. 120, no. 3, pp. 656–663, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. M. Van Engeland, M. P. Weijenberg, G. M. J. M. Roemen et al., “Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer,” Cancer Research, vol. 63, no. 12, pp. 3133–3137, 2003. View at Google Scholar · View at Scopus
  58. K. Curtin, M. L. Slattery, C. M. Ulrich et al., “Genetic polymorphisms in one-carbon metabolismml: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet,” Carcinogenesis, vol. 28, no. 8, pp. 1672–1679, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. K. Curtin, W. Samowitz, C. Ulrich et al., “Nutrients in folate-mediated, one-carbon metabolism and risk of rectal tumors in men and women,” Nutrition and Cancer, vol. 31, no. 1, 2011. View at Google Scholar
  60. A. Hazra, C. S. Fuchs, T. Kawasaki, G. J. Kirkner, D. J. Hunter, and S. Ogino, “Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer,” Cancer Causes and Control, vol. 21, no. 3, pp. 331–345, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. S. De Vogel, K. A. D. Wouters, R. W. H. Gottschalk et al., “Genetic variants of methyl metabolizing enzymes and epigenetic regulators: associations with promoter CpG island hypermethylation in colorectal cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 11, pp. 3086–3096, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. K. Curtin, W. S. Samowitz, R. K. Wolff et al., “MSH6 G39E polymorphism and CpG island methylator phenotype in colon cancer,” Molecular Carcinogenesis, vol. 48, no. 11, pp. 989–994, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. W. S. Samowitz, K. Curtin, R. K. Wolff et al., “The MLH1 93G>A promoter polymorphism and genetic and epigenetic alterations in colon cancer,” Genes Chromosomes and Cancer, vol. 47, no. 10, pp. 835–844, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. H. G. Linhart, H. Lin, Y. Yamada et al., “Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing,” Genes and Development, vol. 21, no. 23, pp. 3110–3122, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. K. Nosho, K. Shima, N. Irahara et al., “DNMT3B expression might contribute to CpG island methylator phenotype in colorectal cancer,” Clinical Cancer Research, vol. 15, no. 11, pp. 3663–3671, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. A. E. Ibrahim, M. J. Arends, A. L. Silva et al., “Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression,” Gut, vol. 60, no. 4, pp. 444–508, 2011. View at Google Scholar
  67. S. Ogino, A. T. Chan, C. S. Fuchs, and E. Giovannucci, “Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field,” Gut, vol. 60, no. 3, pp. 397–411, 2011. View at Publisher · View at Google Scholar · View at PubMed
  68. L. A. E. Hughes, P. A. van den Brandt, A. P. de Bruïne et al., “Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms,” PLoS ONE, vol. 4, no. 11, article e7951, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. M. L. Slattery, A. Lundgreen, J. S. Herrick, and R. K. Wolff, “Genetic variation in RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 and risk of colon or rectal cancer,” Mutation Research, vol. 706, no. 1-2, pp. 13–20, 2011. View at Publisher · View at Google Scholar · View at PubMed
  70. M. L. Slattery, K. Curtin, E. M. Poole et al., “Genetic variation in C-reactive protein (CRP) in relation to colon and rectal cancer risk and survival,” International Journal of Cancer, vol. 128, no. 11, pp. 2726–2734, 2011. View at Google Scholar
  71. A. Portela and M. Esteller, “Epigenetic modifications and human disease,” Nature Biotechnology, vol. 28, no. 10, pp. 1057–1068, 2010. View at Publisher · View at Google Scholar · View at PubMed
  72. M. Esteller, “Epigenetic gene silencing in cancer: the DNA hypermethylome,” Human Molecular Genetics, vol. 16, no. 1, pp. R50–R59, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. J. Frigola, J. Song, C. Stirzaker, R. A. Hinshelwood, M. A. Peinado, and S. J. Clark, “Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band,” Nature Genetics, vol. 38, no. 5, pp. 540–549, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. J. J. Wong, N. J. Hawkins, R. L. Ward, and M. P. Hitchins, “Methylation of the 3p22 region encompassing MLH1 is representative of the CpG island methylator phenotype in colorectal cancer,” Modern Pathology, vol. 24, pp. 396–411, 2011. View at Publisher · View at Google Scholar · View at PubMed
  75. R. A. Irizarry, C. Ladd-Acosta, B. Wen et al., “The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores,” Nature Genetics, vol. 41, no. 2, pp. 178–186, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. P. Malik, N. Zuleger, and E. C. Schirmer, “Nuclear envelope influences on genome organization,” Biochemical Society Transactions, vol. 38, no. 1, pp. 268–272, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. H. P. Easwaran, L. Van Neste, L. Cope et al., “Aberrant silencing of cancer-related genes by CpG hypermethylation occurs independently of their spatial organization in the nucleus,” Cancer Research, vol. 70, no. 20, pp. 8015–8024, 2010. View at Publisher · View at Google Scholar · View at PubMed
  78. J. E. Ohm, K. M. McGarvey, X. Yu et al., “A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing,” Nature Genetics, vol. 39, no. 2, pp. 237–242, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. Y. Schlesinger, R. Straussman, I. Keshet et al., “Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer,” Nature Genetics, vol. 39, no. 2, pp. 232–236, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. H. P. Mohammad, Y. Cai, K. M. McGarvey et al., “Polycomb CBX7 promotes initiation of heritable repression of genes frequently silenced with cancer-specific DNA hypermethylation,” Cancer Research, vol. 69, no. 15, pp. 6322–6330, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. J. P. J. Issa and H. M. Kantarjian, “Targeting DNA methylation,” Clinical Cancer Research, vol. 15, no. 12, pp. 3938–3946, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. J. Kaiser, “Epigenetic drugs take on cancer,” Science, vol. 330, no. 6004, pp. 576–578, 2010. View at Publisher · View at Google Scholar · View at PubMed
  83. J. E. Ohm, P. Mali, L. Van Neste et al., “Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells,” Cancer Research, vol. 70, no. 19, pp. 7662–7673, 2010. View at Publisher · View at Google Scholar · View at PubMed