| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Medical Oncology,
* Dana-Farber Cancer Institute, Boston; Departments of Pathology
and Medicine,
Brigham and Women’s Hospital, Boston; and Harvard Medical School,
Boston, Massachusetts
The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation seems to be a distinct epigenotype of colorectal cancer. However, no study has comprehensively examined features of colorectal cancer with less extensive promoter methylation (designated as "CIMP-low"). Using real-time polymerase chain reaction (MethyLight), we quantified DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1] in 840 relatively unbiased, population-based colorectal cancer samples, obtained from two large prospective cohort studies. CIMP-low (defined as 1/5 to 3/5 methylated promoters) colorectal cancers were significantly more common among men (38 versus 30% in women, P = 0.01) and among KRAS-mutated tumors (44 versus 30% in KRAS/BRAF wild-type tumors, P = 0.0003; 19% in BRAF-mutated tumors, P < 0.0001). In addition, KRAS mutations were significantly more common in CIMP-low tumors (47%) than in CIMP-high tumors (with 
4/5 methylated promoters, 12%, P < 0.0001) and CIMP-0 tumors (with 0/5 methylated promoters, 37%, P = 0.007). The associations of CIMP-low tumors with male sex and KRAS mutations still existed after tumors were stratified by microsatellite instability status. In conclusion, CIMP-low colorectal cancer is associated with male sex and KRAS mutations. The hypothesis that CIMP-low tumors are different from CIMP-high and CIMP-0 tumors needs to be tested further.
This article has been cited by other articles:
 |
|
 |
|
  A. R. Sepulveda, D. Jones, S. Ogino, W. Samowitz, M. L. Gulley, R. Edwards, V. Levenson, V. M. Pratt, B. Yang, K. Nafa, et al. CpG Methylation Analysis--Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics: A Report of the Association for Molecular Pathology J. Mol. Diagn., July 1, 2009; 11(4): 266 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, K. Nosho, N. Irahara, S. Kure, K. Shima, Y. Baba, S. Toyoda, L. Chen, E. L. Giovannucci, J. A. Meyerhardt, et al. A Cohort Study of Cyclin D1 Expression and Prognosis in 602 Colon Cancer Cases Clin. Cancer Res., July 1, 2009; 15(13): 4431 - 4438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, K. Shima, K. Nosho, N. Irahara, Y. Baba, B. M. Wolpin, E. L. Giovannucci, J. A. Meyerhardt, and C. S. Fuchs A Cohort Study of p27 Localization in Colon Cancer, Body Mass Index, and Patient Survival Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1849 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nosho, K. Shima, N. Irahara, S. Kure, Y. Baba, G. J. Kirkner, L. Chen, S. Gokhale, A. Hazra, D. Spiegelman, et al. DNMT3B Expression Might Contribute to CpG Island Methylator Phenotype in Colorectal Cancer Clin. Cancer Res., June 1, 2009; 15(11): 3663 - 3671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, K. Nosho, G. J. Kirkner, K. Shima, N. Irahara, S. Kure, A. T. Chan, J. A. Engelman, P. Kraft, L. C. Cantley, et al. PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer J. Clin. Oncol., March 20, 2009; 27(9): 1477 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pichler, M. Balic, E. Stadelmeyer, C. Ausch, M. Wild, C. Guelly, T. Bauernhofer, H. Samonigg, G. Hoefler, and N. Dandachi Evaluation of High-Resolution Melting Analysis as a Diagnostic Tool to Detect the BRAF V600E Mutation in Colorectal Tumors J. Mol. Diagn., March 1, 2009; 11(2): 140 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, K. Nosho, G. J Kirkner, T. Kawasaki, J. A Meyerhardt, M. Loda, E. L Giovannucci, and C. S Fuchs CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer Gut, January 1, 2009; 58(1): 90 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, G. J. Kirkner, K. Nosho, N. Irahara, S. Kure, K. Shima, A. Hazra, A. T. Chan, R. Dehari, E. L. Giovannucci, et al. Cyclooxygenase-2 Expression Is an Independent Predictor of Poor Prognosis in Colon Cancer Clin. Cancer Res., December 15, 2008; 14(24): 8221 - 8227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, K. Nosho, J. A. Meyerhardt, G. J. Kirkner, A. T. Chan, T. Kawasaki, E. L. Giovannucci, M. Loda, and C. S. Fuchs Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer J. Clin. Oncol., December 10, 2008; 26(35): 5713 - 5720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, K. Nosho, G. J. Kirkner, T. Kawasaki, A. T. Chan, E. S. Schernhammer, E. L. Giovannucci, and C. S. Fuchs A Cohort Study of Tumoral LINE-1 Hypomethylation and Prognosis in Colon Cancer J Natl Cancer Inst, December 3, 2008; 100(23): 1734 - 1738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barault, C. Charon-Barra, V. Jooste, M. F. de la Vega, L. Martin, P. Roignot, P. Rat, A.-M. Bouvier, P. Laurent-Puig, J. Faivre, et al. Hypermethylator Phenotype in Sporadic Colon Cancer: Study on a Population-Based Series of 582 Cases Cancer Res., October 15, 2008; 68(20): 8541 - 8546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Imai and H. Yamamoto Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics Carcinogenesis, April 1, 2008; 29(4): 673 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino and A. Goel Molecular Classification and Correlates in Colorectal Cancer J. Mol. Diagn., January 1, 2008; 10(1): 13 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, T. Kawasaki, G. J Kirkner, Y. Suemoto, J. A Meyerhardt, and C. S Fuchs Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer Gut, November 1, 2007; 56(11): 1564 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shen, P. J. Catalano, A. B. Benson III, 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 Clin. Cancer Res., October 15, 2007; 13(20): 6093 - 6098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Spittle, M. R. Ward, K. L. Nathanson, P. A. Gimotty, E. Rappaport, M. S. Brose, A. Medina, R. Letrero, M. Herlyn, and R. H. Edwards Application of a BRAF Pyrosequencing Assay for Mutation Detection and Copy Number Analysis in Malignant Melanoma J. Mol. Diagn., September 1, 2007; 9(4): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, A. Hazra, G. J. Tranah, G. J. Kirkner, T. Kawasaki, K. Nosho, M. Ohnishi, Y. Suemoto, J. A. Meyerhardt, D. J. Hunter, et al. MGMT germline polymorphism is associated with somatic MGMT promoter methylation and gene silencing in colorectal cancer Carcinogenesis, September 1, 2007; 28(9): 1985 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Samowitz The CpG Island Methylator Phenotype in Colorectal Cancer J. Mol. Diagn., July 1, 2007; 9(3): 281 - 283. [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, T. Kawasaki, G. J. Kirkner, P. Kraft, M. Loda, and C. S. Fuchs Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample J. Mol. Diagn., July 1, 2007; 9(3): 305 - 314. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
