Gastroenterology
Volume 132, Issue 1 , Pages 127-138 , January 2007

The CpG Island Methylator Phenotype and Chromosomal Instability Are Inversely Correlated in Sporadic Colorectal Cancer

  • Ajay Goel

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine and the Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
    • Corresponding Author InformationAddress requests for reprints to: Ajay Goel, PhD, Baylor University Medical Center, 3500 Gaston Avenue, Gastrointestinal Cancer Research Laboratory, Suite H-250, Dallas, Texas 75246. fax: (214) 818-9292
  • ,
  • Takeshi Nagasaka

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine and the Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas
  • ,
  • Christian N. Arnold

      Affiliations

    • University of Freiburg, Department of Internal Medicine, Division of Gastroenterology, Freiburg, Germany
  • ,
  • Toru Inoue

      Affiliations

    • Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
  • ,
  • Cody Hamilton

      Affiliations

    • Institute for Health Care Research and Improvement, Baylor University Medical Center, Dallas, Texas
  • ,
  • Donna Niedzwiecki

      Affiliations

    • CALGB Statistical Center, Duke University Medical Center, Durham, North Carolina
  • ,
  • Carolyn Compton

      Affiliations

    • Department of Pathology, McGill University, Montreal, Canada
  • ,
  • Robert J. Mayer

      Affiliations

    • Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts
  • ,
  • Richard Goldberg

      Affiliations

    • University of North Carolina-Chapel Hill, Chapel Hill, North Carolina
    • Corresponding Author InformationC. Richard Boland, MD, Baylor University Medical Center, 3500 Gaston Avenue, Gastrointestinal Cancer Research Laboratory, Suite H-250, Dallas, Texas 75246. fax: (214) 818-9292.
  • ,
  • Monica M. Bertagnolli

      Affiliations

    • Brigham and Women’s Hospital, Boston, Massachusetts
  • ,
  • C. Richard Boland

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine and the Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas

Received 25 May 2006 ,Accepted 31 August 2006.

References 

  1. Loeb LA. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991;51:3075–3079
  2. Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997;386:623–627
  3. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, et al. 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 Res. 1997;57:808–811
  4. Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res. 1998;72:141–196
  5. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet. 1999;21:163–167
  6. Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, et al. Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res. 2003;63:1608–1614
  7. Rashid A, Issa JP. CpG island methylation in gastroenterologic neoplasia: a maturing field. Gastroenterology. 2004;127:1578–1588
  8. Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4:988–993
  9. Jass JR. Serrated adenoma of the colorectum and the DNA-methylator phenotype. Nat Clin Pract Oncol. 2005;2:398–405
  10. Samowitz WS, Albertsen H, Herrick J, Levin TR, Sweeney C, Murtaugh MA, et al. Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology. 2005;129:837–845
  11. Ogino S, Cantor M, Kawasaki T, Brahmandam M, Kirkner G, Weisenberger DJ, et al. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterized by quantitative DNA methylation analysis and prospective cohort studies. Gut. 2006;55:1000–1006
  12. Yamashita K, Dai T, Dai Y, Yamamoto F, Perucho M. Genetics supersedes epigenetics in colon cancer phenotype. Cancer Cell. 2003;4:121–131
  13. Anacleto C, Leopoldino AM, Rossi B, Soares FA, Lopes A, Rocha JC, et al. Colorectal cancer “methylator phenotype”: fact or artifact?. Neoplasia. 2005;7:331–335
  14. Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, et al. Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell. 2006;9:199–207
  15. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96:8681–8686
  16. Toyota M, Ohe-Toyota M, Ahuja N, Issa JP. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci U S A. 2000;97:710–715
  17. Hawkins N, Norrie M, Cheong K, Mokany E, Ku SL, Meagher A, et al. CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability. Gastroenterology. 2002;122:1376–1387
  18. Nagasaka T, Sasamoto H, Notohara K, Cullings HM, Takeda M, Kimura K, et al. Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol. 2004;22:4584–4594
  19. van Rijnsoever M, Grieu F, Elsaleh H, Joseph D, Iacopetta B. Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands. Gut. 2002;51:797–802
  20. Samowitz WS, Holden JA, Curtin K, Edwards SL, Walker AR, Lin HA, et al. Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer. Am J Pathol. 2001;158:1517–1524
  21. Jones PA. DNA methylation errors and cancer. Cancer Res. 1996;56:2463–2467
  22. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. 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 Res. 1998;58:5248–5257
  23. Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, et al. Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol. 2001;159:2107–2116
  24. Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 2003;63:4561–4567
  25. Toyota M, Issa JP. CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol. 1999;9:349–357
  26. Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59:5438–5442
  27. Goel A, Arnold CN, Tassone P, Chang DK, Niedzwiecki D, Dowell JM, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers. Int J Cancer. 2004;112:754–759
  28. Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 2004;64:3014–3021
  29. Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, et al. APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther. 2004;3:960–964
  30. Goel A, Li M-S, Nagasaka T, Shin SK, Fuerst F, Ricciardiello L, et al. Association of JC Virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroenterology. 2006;130:1950–1961
  31. Lee S, Lee HJ, Kim JH, Lee HS, Jang JJ, Kang GH. Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am J Pathol. 2003;163:1371–1378
  32. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996;93:9821–9826
  33. Chan AO, Issa JP, Morris JS, Hamilton SR, Rashid A. Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol. 2002;160:529–536
  34. Matsuzaki K, Deng G, Tanaka H, Kakar S, Miura S, Kim YS. The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin Cancer Res. 2005;11:8564–8569
  35. Kim HC, Roh SA, Ga IH, Kim JS, Yu CS, Kim JC. CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer. J Gastroenterol Hepatol. 2005;20:1920–1926
  36. Ward RL, Cheong K, Ku SL, Meagher A, O’Connor T, Hawkins NJ. Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability. J Clin Oncol. 2003;21:3729–3736

 Supported by a grant from the NIH (RO1-CA 72851; to C.R.B.), an American Cancer Society-IRG award (to A.G), and a grant from Dr. Mildred-Scheel-Stiftung, Germany (to C.N.A.); and research for CALGB 9865 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, Chairman).The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.Please see Appendix for participating institutes.

PII: S0016-5085(06)02078-6

doi: 10.1053/j.gastro.2006.09.018

Gastroenterology
Volume 132, Issue 1 , Pages 127-138 , January 2007