| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology,*
Leukemia,
andBiostatistics,
University of Texas M. D.Anderson Cancer Center, Houston, Texas
The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. The causes of CIMP are unknown. We studied CIMP in hyperplastic polyps (HPs), with emphasis on patients with multiple HPs (5 to 10 HPs), large HPs (one HP >1 cm) or hyperplastic polyposis (>20 HPs). Methylation of p16, MINT1, MINT2, MINT31, and hMLH1 was analyzed by methylation-specific polymerase chain reaction in 102 HPs, 8 serrated adenomas, 19 tubular adenomas, and 9 adenocarcinomas from 17 patients, with multiple/large HPs or hyperplastic polyposis and in 16 sporadic HPs from 14 additional patients. Sporadic HPs were CIMP-negative (not methylated at any locus), but 43% of HPs from multiple/large HPs, or hyperplastic polyposis were CIMP-high (two or more methylated loci, P = 0.00001). Methylation among the four loci was correlated within HPs (odds ratio, 3.41; P = 0.002), and the methylation status of HPs within the same patient was also correlated (odds ratio, 5.92; P = 0.0001). CIMP-high HPs were present primarily in patients with a predominance of HPs in the right colon and/or serrated adenomas (P = 0.0009) and were associated with the absence of K-ras proto-oncogene mutations (odds ratio, 5.08; P = 0.03). Our findings of concordant CpG island methylation of HPs in multiple/large HPs or hyperplastic polyposis supports the concept that some patients have a hypermethylator phenotype characterized by methylation of multiple HPs and other colorectal lesions. The hypermethylator phenotype is related to patient-specific factors, such as carcinogenic exposure or genetic predisposition.
This article has been cited by other articles:
 |
|
 |
|
  D. R. English, J. P. Young, J. A. Simpson, M. A. Jenkins, M. C. Southey, M. D. Walsh, D. D. Buchanan, M. A. Barker, A. M. Haydon, S. G. Royce, et al. Ethnicity and Risk for Colorectal Cancers Showing Somatic BRAF V600E Mutation or CpG Island Methylator Phenotype Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1774 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Karpinski, D. Ramsey, Z. Grzebieniak, M. M. Sasiadek, and N. Blin The CpG Island Methylator Phenotype Correlates with Long-Range Epigenetic Silencing in Colorectal Cancer Mol. Cancer Res., April 1, 2008; 6(4): 585 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Al-Ghnaniem, J. Peters, R. Foresti, N. Heaton, and M. Pufulete Methylation of estrogen receptor {alpha} and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1064 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Young, M. Jenkins, S. Parry, B. Young, D. Nancarrow, D. English, G. Giles, and J. Jass Serrated pathway colorectal cancer in the population: genetic consideration Gut, October 1, 2007; 56(10): 1453 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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 J. Mol. Diagn., November 1, 2006; 8(5): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Young and J. R. Jass The case for a genetic predisposition to serrated neoplasia in the colorectum: hypothesis and review of the literature. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1778 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Minoo, K Baker, R Goswami, G Chong, W D Foulkes, A R Ruszkiewicz, M Barker, D Buchanan, J Young, and J R Jass Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis Gut, October 1, 2006; 55(10): 1467 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Ogino, M Cantor, T Kawasaki, M Brahmandam, G J Kirkner, D J Weisenberger, M Campan, P W Laird, M Loda, and C S Fuchs CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies Gut, July 1, 2006; 55(7): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Chan, A. S. Soliman, Q. Zhang, A. Rashid, A. Bedeir, P. S. Houlihan, N. Mokhtar, N. Al-Masri, U. Ozbek, R. Yaghan, et al. Differing DNA Methylation Patterns and Gene Mutation Frequencies in Colorectal Carcinomas from Middle Eastern Countries Clin. Cancer Res., December 1, 2005; 11(23): 8281 - 8287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Ramsey, W. Burke, L. Pinsky, L. Clarke, P. Newcomb, and M. J. Khoury Family History Assessment to Detect Increased Risk for Colorectal Cancer: Conceptual Considerations and a Preliminary Economic Analysis Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2494 - 2500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shen, Y. Kondo, G. L. Rosner, L. Xiao, N. S. Hernandez, J. Vilaythong, P. S. Houlihan, R. S. Krouse, A. R. Prasad, J. G. Einspahr, et al. MGMT Promoter Methylation and Field Defect in Sporadic Colorectal Cancer J Natl Cancer Inst, September 21, 2005; 97(18): 1330 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Beach, A. O.-O. Chan, T.-T. Wu, J. A. White, J. S. Morris, S. Lunagomez, R. R. Broaddus, J.-P. J. Issa, S. R. Hamilton, and A. Rashid BRAF Mutations in Aberrant Crypt Foci and Hyperplastic Polyposis Am. J. Pathol., April 1, 2005; 166(4): 1069 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Petko, M. Ghiassi, A. Shuber, J. Gorham, W. Smalley, M. K. Washington, S. Schultenover, S. Gautam, S. D. Markowitz, and W. M. Grady Aberrantly Methylated CDKN2A, MGMT, and MLH1 in Colon Polyps and in Fecal DNA from Patients with Colorectal Polyps Clin. Cancer Res., February 1, 2005; 11(3): 1203 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Zauber, M Sabbath-Solitare, S Marotta, A Zauber, and T Bishop Comparative molecular pathology of sporadic hyperplastic polyps and neoplastic lesions from the same individual J. Clin. Pathol., October 1, 2004; 57(10): 1084 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Belshaw, G. O. Elliott, E. A. Williams, D. M. Bradburn, S. J. Mills, J. C. Mathers, and I. T. Johnson Use of DNA from Human Stools to Detect Aberrant CpG Island Methylation of Genes Implicated in Colorectal Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1495 - 1501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Higuchi and J R Jass My approach to serrated polyps of the colorectum J. Clin. Pathol., July 1, 2004; 57(7): 682 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C V A Wynter, M D Walsh, T Higuchi, B A Leggett, J Young, and J R Jass Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer Gut, April 1, 2004; 53(4): 573 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopelovich, J. A. Crowell, and J. R. Fay The Epigenome as a Target for Cancer Chemoprevention J Natl Cancer Inst, December 3, 2003; 95(23): 1747 - 1757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Frazier, L. Xi, J. Zong, N. Viscofsky, A. Rashid, E. F. Wu, P. M. Lynch, C. I. Amos, and J.-P. J. Issa Association of the CpG Island Methylator Phenotype with Family History of Cancer in Patients with Colorectal Cancer Cancer Res., August 15, 2003; 63(16): 4805 - 4808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Chan, W. Zhao, Cancer Genome Project, S. Y. Leung, and S. T. Yuen BRAF and KRAS Mutations in Colorectal Hyperplastic Polyps and Serrated Adenomas Cancer Res., August 15, 2003; 63(16): 4878 - 4881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Kaneko, S Sakurai, M Hironaka, S Sato, S Oguni, Y Sakuma, K Sato, K Sugano, and K Saito Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas Gut, May 1, 2003; 52(5): 641 - 646. [Abstract] [Full Text]
|
|
|
|
|
|
C. Bariol, C. Suter, K. Cheong, S.-L. Ku, A. Meagher, N. Hawkins, and R. Ward The Relationship between Hypomethylation and CpG Island Methylation in Colorectal Neoplasia Am. J. Pathol., April 1, 2003; 162(4): 1361 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. MOORE, W.-Y. HUANG, J. CHUNG, and R. B. HAYES Epidemiologic Considerations to Assess Altered DNA Methylation from Environmental Exposures in Cancer Ann. N.Y. Acad. Sci., March 1, 2003; 983(1): 181 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Jass Serrated Adenoma of the Colorectum: A Lesion with Teeth Am. J. Pathol., March 1, 2003; 162(3): 705 - 708. [Full Text] [PDF]
|
|
|
|
|
|
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 Am. J. Pathol., March 1, 2003; 162(3): 815 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O.-O. Chan, R. R. Broaddus, P. S. Houlihan, J.-P. J. Issa, S. R. Hamilton, and A. Rashid CpG Island Methylation in Aberrant Crypt Foci of the Colorectum Am. J. Pathol., May 1, 2002; 160(5): 1823 - 1830. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
