Genetic and Epigenetic Pathways to Colon Cancer Relating Experimental Evidence with Modeling

  • Natalia L. Komarova
  • Dominik Wodarz
  • C. Richard Boland
  • Ajay Goel
Part of the Modeling and Simulation in Science, Engineering and Technology book series (MSSET)


Lynch Syndrome Microsatellite Instability Familial Adenomatous Polyposis Patient Sporadic Colorectal Cancer Epigenetic Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ahuja, N., Mohan, A.L., Li, Q., Stolker, J.M., Herman, J.G., Hamilton, S.R., Baylin, S.B., Issa, J.P.: Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res57(16), 3370–3374 (1997)Google Scholar
  2. 2.
    Albertini, R.J., Nicklas, J.A., O’Neill, J.P., Robison, S.H.: In vivo somatic mutations in humans: measurement and analysis. Annu Rev Genet24, 305–326 (1990)Google Scholar
  3. 3.
    Alexander, J., Watanabe, T., Wu, T.T., Rashid, A., Li, S., Hamilton, S.R.: Histopathological identification of colon cancer with microsatellite instability. Am J Pathol158(2), 527–535 (2001)Google Scholar
  4. 4.
    Araten, D.J., Golde, D.W., Zhang, R.H., Thaler, H.T., Gargiulo, L., Notaro, R., Luzzatto, L.: A quantitative measurement of the human somatic mutation rate. Cancer Res65(18), 8111–8117 (2005)CrossRefGoogle Scholar
  5. 5.
    Bach, S.P., Renehan, A.G., Potten, C.S.: Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis21(3), 469–476 (2000)CrossRefGoogle Scholar
  6. 6.
    Bardelli, A., Cahill, D.P., Lederer, G., Speicher, M.R., Kinzler, K.W., Vogelstein, B., Lengauer, C.: Carcinogen-specific induction of genetic instability. Proc Natl Acad Sci USA98(10), 5770–5775 (2001)CrossRefGoogle Scholar
  7. 7.
    Bernheim, J.L., Mendelsohn, J., Kelley, M.F., Dorian, R.: Kinetics of cell death and disintegration in human lymphocyte cultures. Proc Natl Acad Sci USA74(6), 2536–2540 (1977)CrossRefGoogle Scholar
  8. 8.
    Bird, A.: DNA methylation patterns and epigenetic memory. Genes Dev16(1), 6–21 (2002)MathSciNetCrossRefGoogle Scholar
  9. 9.
    Bird, A.P., Wolffe, A.P.: Methylation-induced repression—belts, braces, and chromatin. Cell99(5), 451–454 (1999)CrossRefGoogle Scholar
  10. 10.
    Bischoff, J.R., Anderson, L., Zhu, Y., Mossie, K., Ng, L., Souza, B., Schryver, B., Flanagan, P., Clairvoyant, F., Ginther, C., Chan, C.S., Novotny, M., Slamon, D.J., Plowman, G.D.: A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J17(11), 3052–3065 (1998). Comparative StudyCrossRefGoogle Scholar
  11. 11.
    Boland, C.R., Thibodeau, S.N., Hamilton, S.R., Sidransky, D., Eshleman, J.R., Burt, R.W., Meltzer, S.J., Rodriguez-Bigas, M.A., Fodde, R., Ranzani, G.N., Srivastava, S.: A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res58(22), 5248–5257 (1998). Consensus Development ConferenceGoogle Scholar
  12. 12.
    Cahill, D.P., Kinzler, K.W., Vogelstein, B., Lengauer, C.: Genetic instability and darwinian selection in tumours. Trends Cell Biol9(12), 57–60 (1999)CrossRefGoogle Scholar
  13. 13.
    Cahill, D.P., Lengauer, C., Yu, J., Riggins, G.J., Willson, J.K., Markowitz, S.D., Kinzler, K.W., Vogelstein, B.: Mutations of mitotic checkpoint genes in human cancers. Nature392(6673), 300–303 (1998)CrossRefGoogle Scholar
  14. 14.
    Chan, A.O.O., Issa, J.P., Morris, J.S., Hamilton, S.R., Rashid, A.: Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol160(2), 529–536 (2002)Google Scholar
  15. 15.
    de la Chapelle, A.: Genetic predisposition to colorectal cancer. Nat Rev Cancer4(10), 769–780 (2004)CrossRefGoogle Scholar
  16. 16.
    Chu, K., Leonhardt, E.A., Trinh, M., Prieur-Carrillo, G., Lindqvist, J., Albright, N., Ling, C.C., Dewey, W.C.: Computerized video time-lapse (CVTL) analysis of cell death kinetics in human bladder carcinoma cells (EJ30) Xirradiated in different phases of the cell cycle. Radiat Res158(6), 667–677 (2002)CrossRefGoogle Scholar
  17. 17.
    Clahsen, P.C., van de Velde, C.J., Duval, C., Pallud, C., Mandard, A.M., Delobelle-Deroide, A., van den Broek, L., van de Vijver, M.J.: The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol25(4), 356–363 (1999)CrossRefGoogle Scholar
  18. 18.
    Cunningham, J.M., Christensen, E.R., Tester, D.J., Kim, C.Y., Roche, P.C., Burgart, L.J., Thibodeau, S.N.: Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res58(15), 3455–3460 (1998)Google Scholar
  19. 19.
    Drake, J.W., Charlesworth, B., Charlesworth, D., Crow, J.F.: Rates of spontaneous mutation. Genetics148(4), 1667–1686 (1998)Google Scholar
  20. 20.
    Duesberg, P., Rausch, C., Rasnick, D., Hehlmann, R.: Genetic instability of cancer cells is proportional to their degree of aneuploidy. Proc Natl Acad Sci USA95(23), 13,692–13,697 (1998)CrossRefGoogle Scholar
  21. 21.
    Eshleman, J.R., Casey, G., Kochera, M.E., Sedwick, W.D., Swinler, S.E., Veigl, M.L., Willson, J.K., Schwartz, S., Markowitz, S.D.: Chromosome number and structure both are markedly stable in RER colorectal cancers and are not destabilized by mutation of p53. Oncogene17(6), 719–725 (1998). Comparative StudyCrossRefGoogle Scholar
  22. 22.
    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., Herman, J.G.: DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet10(26), 3001–3007 (2001)CrossRefGoogle Scholar
  23. 23.
    Fearon, E.R., Vogelstein, B.: A genetic model for colorectal tumorigenesis. Cell61(5), 759–767 (1990)CrossRefGoogle Scholar
  24. 24.
    Fodde, R., Kuipers, J., Rosenberg, C., Smits, R., Kielman, M., Gaspar, C., van Es, J.H., Breukel, C., Wiegant, J., Giles, R.H., Clevers, H.: Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol3(4), 433–438 (2001)CrossRefGoogle Scholar
  25. 25.
    Fodde, R., Smits, R., Clevers, H.: APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer1(1), 55–67 (2001)CrossRefGoogle Scholar
  26. 26.
    Foster, P.L.: Sorting out mutation rates. Proc Natl Acad Sci USA96(14), 7617–7618 (1999). CommentCrossRefGoogle Scholar
  27. 27.
    Fraizer, G.C., Diaz, M.F., Lee, I.L., Grossman, H.B., Sen, S.: Aurora- A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. Int J Oncol25(6), 1631–1639 (2004)Google Scholar
  28. 28.
    Giet, R., Petretti, C., Prigent, C.: Aurora kinases, aneuploidy and cancer, a coincidence or a real link? Trends Cell Biol15(5), 241–250 (2005)CrossRefGoogle Scholar
  29. 29.
    Goel, A., Arnold, C.N., Niedzwiecki, D., Chang, D.K., Ricciardiello, L., Carethers, J.M., Dowell, J.M., Wasserman, L., Compton, C., Mayer, R.J., Bertagnolli, M.M., Boland, C.R.: Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res63(7), 1608–1614 (2003)Google Scholar
  30. 30.
    Goel, A., Li, M.S., Nagasaka, T., Shin, S.K., Fuerst, F., Ricciardiello, L., Wasserman, L., Boland, C.R.: Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroenterology130(7), 1950–1961 (2006). Comparative StudyCrossRefGoogle Scholar
  31. 31.
    Goel, A., Nagasaka, T., Arnold, C.N., Inoue, T., Hamilton, C., Niedzwiecki, D., Compton, C., Mayer, R.J., Goldberg, R., Bertagnolli, M.M., Boland, C.R.: The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology132(1), 127–138 (2007)CrossRefGoogle Scholar
  32. 32.
    Goodson, W.H., Moore, D.H., Ljung, B.M., Chew, K., Florendo, C., Mayall, B., Smith, H.S., Waldman, F.M.: The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer. Breast Cancer Res Treat49(2), 155–164 (1998). Comparative StudyCrossRefGoogle Scholar
  33. 33.
    Grady, W.M.: Genomic instability and colon cancer. Cancer Metastasis Rev23(1-2), 11–27 (2004)CrossRefGoogle Scholar
  34. 34.
    Gratzner, H.G.: Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science218(4571), 474–475 (1982)CrossRefGoogle Scholar
  35. 35.
    Gryfe, R., Kim, H., Hsieh, E.T., Aronson, M.D., Holowaty, E.J., Bull, S.B., Redston, M., Gallinger, S.: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med342(2), 69–77 (2000). Comparative StudyCrossRefGoogle Scholar
  36. 36.
    Hawkins, N., Norrie, M., Cheong, K., Mokany, E., Ku, S.L., Meagher, A., O’Connor, T., Ward, R.: CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability. Gastroenterology122(5), 1376–1387 (2002)CrossRefGoogle Scholar
  37. 37.
    Henderson, B.W., Waldow, S.M., Mang, T.S., Potter, W.R., Malone, P.B., Dougherty, T.J.: Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res45(2), 572–576 (1985)Google Scholar
  38. 38.
    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.: Silencing of the VHL tumorsuppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA91(21), 9700–9704 (1994)CrossRefGoogle Scholar
  39. 39.
    Hontz, A.E., Li, S.A., Lingle, W.L., Negron, V., Bruzek, A., Salisbury, J.L., Li, J.J.: Aurora a and B overexpression and centrosome amplification in early estrogen-induced tumor foci in the Syrian hamster kidney: implications for chromosomal instability, aneuploidy, and neoplasia. Cancer Res67(7), 2957–2963 (2007)CrossRefGoogle Scholar
  40. 40.
    Huang, J., Papadopoulos, N., McKinley, A.J., Farrington, S.M., Curtis, L.J., Wyllie, A.H., Zheng, S., Willson, J.K., Markowitz, S.D., Morin, P., Kinzler, K.W., Vogelstein, B., Dunlop, M.G.: APC mutations in colorectal tumors with mismatch repair deficiency. Proc Natl Acad Sci USA93(17), 9049–9054 (1996). Comparative StudyCrossRefGoogle Scholar
  41. 41.
    Issa, J.P.: Methylation and prognosis: of molecular clocks and hypermethylator phenotypes. Clin Cancer Res9(8), 2879–2881 (2003). CommentGoogle Scholar
  42. 42.
    Issa, J.P.: CpG island methylator phenotype in cancer. Nat Rev Cancer4(12), 988–993 (2004)CrossRefGoogle Scholar
  43. 43.
    Jass, J.R.: Serrated adenoma of the colorectum: a lesion with teeth. Am J Pathol162(3), 705–708 (2003). CommentGoogle Scholar
  44. 44.
    Jass, J.R.: Serrated adenoma of the colorectum and the DNA-methylator phenotype. Nat Clin Pract Oncol2(8), 398–405 (2005)CrossRefGoogle Scholar
  45. 45.
    Jass, J.R.: Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology50(1), 113–130 (2007)CrossRefGoogle Scholar
  46. 46.
    Jass, J.R., Biden, K.G., Cummings, M.C., Simms, L.A., Walsh, M., Schoch, E., Meltzer, S.J., Wright, C., Searle, J., Young, J., Leggett, B.A.: Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways. J Clin Pathol52(6), 455–460 (1999)CrossRefGoogle Scholar
  47. 47.
    Kambara, T., Simms, L.A., Whitehall, V.L.J., Spring, K.J., Wynter, C.V.A., Walsh, M.D., Barker, M.A., Arnold, S., McGivern, A., Matsubara, N., Tanaka, N., Higuchi, T., Young, J., Jass, J.R., Leggett, B.A.: BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut53(8), 1137–1144 (2004)CrossRefGoogle Scholar
  48. 48.
    Kane, M.F., Loda, M., Gaida, G.M., Lipman, J., Mishra, R., Goldman, H., Jessup, J.M., Kolodner, R.: Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res57(5), 808–811 (1997)Google Scholar
  49. 49.
    Keller, J.J., Offerhaus, G.J., Drillenburg, P., Caspers, E., Musler, A., Ristimaki, A., Giardiello, F.M.: Molecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis. Clin Cancer Res7(12), 4000–4007 (2001)Google Scholar
  50. 50.
    Komarova, N.L., Lengauer, C., Vogelstein, B., Nowak, M.A.: Dynamics of genetic instability in sporadic and familial colorectal cancer. Cancer Biol Ther1(6), 685–692 (2002)Google Scholar
  51. 51.
    Komarova, N.L., Sengupta, A., Nowak, M.A.: Mutation-selection networks of cancer initiation: tumor suppressor genes and chromosomal instability. J Theor Biol223(4), 433–450 (2003)MathSciNetCrossRefGoogle Scholar
  52. 52.
    Kondo, Y., Issa, J.P.: Epigenetic changes in colorectal cancer. Cancer Metastasis Rev23(1-2), 29–39 (2004)CrossRefGoogle Scholar
  53. 53.
    Kumar, S., Subramanian, S.: Mutation rates in mammalian genomes. Proc Natl Acad Sci USA99(2), 803–808 (2002)CrossRefGoogle Scholar
  54. 54.
    Laghi, L., Randolph, A.E., Chauhan, D.P., Marra, G., Major, E.O., Neel, J.V., Boland, C.R.: JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA96(13), 7484–7489 (1999)CrossRefGoogle Scholar
  55. 55.
    Lamlum, H., Ilyas, M., Rowan, A., Clark, S., Johnson, V., Bell, J., Frayling, I., Efstathiou, J., Pack, K., Payne, S., Roylance, R., Gorman, P., Sheer, D., Neale, K., Phillips, R., Talbot, I., Bodmer, W., Tomlinson, I.: The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson’s ’two-hit’ hypothesis. Nat Med5(9), 1071–1075 (1999)CrossRefGoogle Scholar
  56. 56.
    Lengauer, C.: Cancer. An unstable liaison. Science300(5618), 442–443 (2003). CommentCrossRefGoogle Scholar
  57. 57.
    Lengauer, C., Kinzler, K.W., Vogelstein, B.: DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci USA94(6), 2545–2550 (1997)CrossRefGoogle Scholar
  58. 58.
    Lengauer, C., Kinzler, K.W., Vogelstein, B.: Genetic instability in colorectal cancers. Nature386(6625), 623–627 (1997)CrossRefGoogle Scholar
  59. 59.
    Lengauer, C., Kinzler, K.W., Vogelstein, B.: Genetic instabilities in human cancers. Nature396(6712), 643–649 (1998)CrossRefGoogle Scholar
  60. 60.
    Li, E.: Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet3(9), 662–673 (2002)CrossRefGoogle Scholar
  61. 61.
    Macaluso, M., Giordano, A.: How does DNA methylation mark the fate of cells? Tumori90(4), 367–372 (2004)Google Scholar
  62. 62.
    Markowitz, S., Wang, J., Myeroff, L., Parsons, R., Sun, L., Lutterbaugh, J., Fan, R.S., Zborowska, E., Kinzler, K.W., Vogelstein, B.: Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science268(5215), 1336–1338 (1995). CommentCrossRefGoogle Scholar
  63. 63.
    Matsuzaki, K., Deng, G., Tanaka, H., Kakar, S., Miura, S., Kim, Y.S.: The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin Cancer Res11(24 Pt 1), 8564–8569 (2005)Google Scholar
  64. 64.
    Misell, L.M., Hwang, E.S., Au, A., Esserman, L., Hellerstein, M.K.: Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans. Breast Cancer Res Treat89(3), 257–264 (2005). Comparative StudyCrossRefGoogle Scholar
  65. 65.
    Mori, Y., Sato, F., Selaru, F.M., Olaru, A., Perry, K., Kimos, M.C., Tamura, G., Matsubara, N., Wang, S., Xu, Y., Yin, J., Zou, T.T., Leggett, B., Young, J., Nukiwa, T., Stine, O.C., Abraham, J.M., Shibata, D., Meltzer, S.J.: Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers. Cancer Res62(13), 3641–3645 (2002). Comparative StudyGoogle Scholar
  66. 66.
    Nagasaka, T., Sasamoto, H., Notohara, K., Cullings, H.M., Takeda, M., Kimura, K., Kambara, T., MacPhee, D.G., Young, J., Leggett, B.A., Jass, J.R., Tanaka, N., Matsubara, N.: Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol22(22), 4584–4594 (2004)CrossRefGoogle Scholar
  67. 67.
    Neese, R.A., Misell, L.M., Turner, S., Chu, A., Kim, J., Cesar, D., Hoh, R., Antelo, F., Strawford, A., McCune, J.M., Christiansen, M., Hellerstein, M.K.: Measurement in vivo of proliferation rates of slow turnover cells by 2H2O labeling of the deoxyribose moiety of DNA. Proc Natl Acad Sci USA99(24), 15,345–15,350 (2002). Comparative StudyCrossRefGoogle Scholar
  68. 68.
    Nishida, N., Nagasaka, T., Kashiwagi, K., Boland, C., Goel, A.: High copy amplification of the aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther6(4) (2007)Google Scholar
  69. 69.
    Nowak, M.A., Komarova, N.L., Sengupta, A., Jallepalli, P.V., Shih, I.M., Vogelstein, B., Lengauer, C.: The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA99(25), 16,226–16,231 (2002)CrossRefGoogle Scholar
  70. 70.
    Ogino, S., Cantor, M., Kawasaki, T., Brahmandam, M., Kirkner, G.J., Weisenberger, D.J., Campan, M., Laird, P.W., Loda, M., Fuchs, C.S.: CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies. Gut55(7), 1000–1006 (2006)CrossRefGoogle Scholar
  71. 71.
    Oller, A.R., Rastogi, P., Morgenthaler, S., Thilly, W.G.: A statistical model to estimate variance in long term-low dose mutation assays: testing of the model in a human lymphoblastoid mutation assay. Mutat Res216(3), 149–161 (1989)Google Scholar
  72. 72.
    Piao, Z., Fang, W., Malkhosyan, S., Kim, H., Horii, A., Perucho, M., Huang, S.: Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. Cancer Res60(17), 4701–4704 (2000)Google Scholar
  73. 73.
    Potten, C.S., Kellett, M., Rew, D.A., Roberts, S.A.: Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli. Gut33(4), 524–529 (1992)CrossRefGoogle Scholar
  74. 74.
    Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K.W., Vogelstein, B., Velculescu, V.E.: Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature418(6901), 934 (2002)CrossRefGoogle Scholar
  75. 75.
    Rajagopalan, H., Lengauer, C.: Aneuploidy and cancer. Nature432(7015), 338–341 (2004)CrossRefGoogle Scholar
  76. 76.
    Rampino, N., Yamamoto, H., Ionov, Y., Li, Y., Sawai, H., Reed, J.C., Perucho, M.: Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science275(5302), 967–969 (1997)CrossRefGoogle Scholar
  77. 77.
    Rashid, A., Issa, J.P.: CpG island methylation in gastroenterologic neoplasia: a maturing field. Gastroenterology127(5), 1578–1588 (2004)CrossRefGoogle Scholar
  78. 78.
    Ribic, C.M., Sargent, D.J., Moore, M.J., Thibodeau, S.N., French, A.J., Goldberg, R.M., Hamilton, S.R., Laurent-Puig, P., Gryfe, R., Shepherd, L.E., Tu, D., Redston, M., Gallinger, S.: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med349(3), 247–257 (2003). Clinical TrialCrossRefGoogle Scholar
  79. 79.
    Ricciardiello, L., Baglioni, M., Giovannini, C., Pariali, M., Cenacchi, G., Ripalti, A., Landini, M.P., Sawa, H., Nagashima, K., Frisque, R.J., Goel, A., Boland, C.R., Tognon, M., Roda, E., Bazzoli, F.: Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res63(21), 7256–7262 (2003)Google Scholar
  80. 80.
    Ricciardiello, L., Laghi, L., Ramamirtham, P., Chang, C.L., Chang, D.K., Randolph, A.E., Boland, C.R.: JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology119(5), 1228–1235 (2000)CrossRefGoogle Scholar
  81. 81.
    van Rijnsoever, M., Grieu, F., Elsaleh, H., Joseph, D., Iacopetta, B.: Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands. Gut51(6), 797–802 (2002)CrossRefGoogle Scholar
  82. 82.
    Rivkin, R.B.: Radioisotopic method for measuring cell division rates of individual species of diatoms from natural populations. Appl Environ Microbiol51(4), 769–775 (1986)Google Scholar
  83. 83.
    Ro, S., Rannala, B.: Methylation patterns and mathematical models reveal dynamics of stem cell turnover in the human colon. Proc Natl Acad Sci USA98(19), 10,519–10,521 (2001). CommentCrossRefGoogle Scholar
  84. 84.
    Robertson, K.D.: DNA methylation and human disease. Nat Rev Genet6(8), 597–610 (2005)CrossRefGoogle Scholar
  85. 85.
    Robertson, K.D., Wolffe, A.P.: DNA methylation in health and disease. Nat Rev Genet1(1), 11–19 (2000)CrossRefGoogle Scholar
  86. 86.
    Rowan, A., Halford, S., Gaasenbeek, M., Kemp, Z., Sieber, O., Volikos, E., Douglas, E., Fiegler, H., Carter, N., Talbot, I., Silver, A., Tomlinson, I.: Refining molecular analysis in the pathways of colorectal carcinogenesis. Clin Gastroenterol Hepatol3(11), 1115–1123 (2005)CrossRefGoogle Scholar
  87. 87.
    Rowan, A.J., Lamlum, H., Ilyas, M., Wheeler, J., Straub, J., Papadopoulou, A., Bicknell, D., Bodmer, W.F., Tomlinson, I.P.: APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits.” Proc Natl Acad Sci USA97(7), 3352–3357 (2000)CrossRefGoogle Scholar
  88. 88.
    Rudolph, P., Alm, P., Heidebrecht, H.J., Bolte, H., Ratjen, V., Baldetorp, B., Ferno, M., Olsson, H., Parwaresch, R.: Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. J Natl Cancer Inst91(3), 271–278 (1999)CrossRefGoogle Scholar
  89. 89.
    Samowitz, W.S., Albertsen, H., Herrick, J., Levin, T.R., Sweeney, C., Murtaugh, M.A., Wolff, R.K., Slattery, M.L.: Evaluation of a large, populationbased sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology129(3), 837–845 (2005)CrossRefGoogle Scholar
  90. 90.
    Samowitz, W.S., Holden, J.A., Curtin, K., Edwards, S.L., Walker, A.R., Lin, H.A., Robertson, M.A., Nichols, M.F., Gruenthal, K.M., Lynch, B.J., Leppert, M.F., Slattery, M.L.: Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer. Am J Pathol158(4), 1517–1524 (2001)Google Scholar
  91. 91.
    Shen, L., Ahuja, N., Shen, Y., Habib, N.A., Toyota, M., Rashid, A., Issa, J.P.: DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst94(10), 755–761 (2002)Google Scholar
  92. 92.
    Shia, J., Ellis, N.A., Paty, P.B., Nash, G.M., Qin, J., Offit, K., Zhang, X.M., Markowitz, A.J., Nafa, K., Guillem, J.G., Wong, W.D., Gerald, W.L., Klimstra, D.S.: Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol27(11), 1407–1417 (2003). Evaluation StudiesCrossRefGoogle Scholar
  93. 93.
    Sidransky, D.: Emerging molecular markers of cancer. Nat Rev Cancer2(3), 210–219 (2002)CrossRefGoogle Scholar
  94. 94.
    Suraweera, N., Duval, A., Reperant, M., Vaury, C., Furlan, D., Leroy, K., Seruca, R., Iacopetta, B., Hamelin, R.: Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology123(6), 1804–1811 (2002)CrossRefGoogle Scholar
  95. 95.
    Thibodeau, S.N., Bren, G., Schaid, D.: Microsatellite instability in cancer of the proximal colon. Science260(5109), 816–819 (1993). CommentCrossRefGoogle Scholar
  96. 96.
    Thor, A.D., Liu, S., Moore, D.H.n., Edgerton, S.M.: Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol17(2), 470–477 (1999). Comparative StudyGoogle Scholar
  97. 97.
    Tomlinson, I., Halford, S., Aaltonen, L., Hawkins, N., Ward, R.: Does MSI-low exist? J Pathol197(1), 6–13 (2002)CrossRefGoogle Scholar
  98. 98.
    Toyota, M., Ahuja, N., Ohe-Toyota, M., Herman, J.G., Baylin, S.B., Issa, J.P.: CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA96(15), 8681–8686 (1999)CrossRefGoogle Scholar
  99. 99.
    Toyota, M., Ahuja, N., Suzuki, H., Itoh, F., Ohe-Toyota, M., Imai, K., Baylin, S.B., Issa, J.P.: Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res59(21), 5438–5442 (1999)Google Scholar
  100. 100.
    Toyota, M., Ohe-Toyota, M., Ahuja, N., Issa, J.P.: Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci USA97(2), 710–715 (2000)CrossRefGoogle Scholar
  101. 101.
    Ueki, T., Toyota, M., Skinner, H., Walter, K.M., Yeo, C.J., Issa, J.P., Hruban, R.H., Goggins, M.: Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma. Cancer Res61(23), 8540–8546 (2001)Google Scholar
  102. 102.
    Waldman, F.M., Chew, K., Ljung, B.M., Goodson, W., Hom, J., Duarte, L.A., Smith, H.S., Mayall, B.: A comparison between bromodeoxyuridine and 3H thymidine labeling in human breast tumors. Mod Pathol4(6), 718–722 (1991). Comparative StudyGoogle Scholar
  103. 103.
    Ward, R.L., Cheong, K., Ku, S.L., Meagher, A., O’Connor, T., Hawkins, N.J.: Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability. J Clin Oncol21(20), 3729–3736 (2003)CrossRefGoogle Scholar
  104. 104.
    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., Laird, P.W.: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet38(7), 787–793 (2006)CrossRefGoogle Scholar
  105. 105.
    Whitehall, V.L.J., Wynter, C.V.A., Walsh, M.D., Simms, L.A., Purdie, D., Pandeya, N., Young, J., Meltzer, S.J., Leggett, B.A., Jass, J.R.: Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer. Cancer Res62(21), 6011–6014 (2002)Google Scholar
  106. 106.
    Wicking, C., Simms, L.A., Evans, T.,Walsh, M., Chawengsaksophak, K., Beck, F., Chenevix-Trench, G., Young, J., Jass, J., Leggett, B., Wainwright, B.: CDX2, a human homologue of Drosophila caudal, is mutated in both alleles in a replication error positive colorectal cancer. Oncogene17(5), 657–659 (1998)CrossRefGoogle Scholar
  107. 107.
    Wodarz, D., Komarova, N.L.: Computational biology of cancer: lecture notes and mathematical modeling. World Scientific, New Jersey, London, Singapore (2005)MATHGoogle Scholar
  108. 108.
    Yamamoto, H., Sawai, H., Weber, T.K., Rodriguez-Bigas, M.A., Perucho, M.: Somatic frameshift mutations in DNA mismatch repair and proapoptosis genes in hereditary nonpolyposis colorectal cancer. Cancer Res58(5), 997–1003 (1998)Google Scholar
  109. 109.
    Yang, A.S., Estecio, M.R.H., Doshi, K., Kondo, Y., Tajara, E.H., Issa, J.P.: A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res32(3), e38 (2004)CrossRefGoogle Scholar
  110. 110.
    Yatabe, Y., Tavare, S., Shibata, D.: Investigating stem cells in human colon by using methylation patterns. Proc Natl Acad Sci USA98(19), 10,839–10,844 (2001)Google Scholar

Copyright information

© Birkhäuser Boston 2008

Authors and Affiliations

  • Natalia L. Komarova
    • 1
  • Dominik Wodarz
    • 2
  • C. Richard Boland
    • 3
  • Ajay Goel
    • 3
  1. 1.Department of MathematicsUniversity of CaliforniaIrvineUSA
  2. 2.Department of Ecology and EvolutionUniversity of CaliforniaIrvineUSA
  3. 3.Department of Internal Medicine Division of Gastroenterology and Charles A. Sammons CancerCenterBaylor University Medical CenterDallasUSA

Personalised recommendations