| 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:
 |
|
 |
|
  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 |
