JMD ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Originally published online as doi:10.2353/jmoldx.2007.060170 on May 3, 2007

Published online before print May 3, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jmoldx.2007.060170v1
9/3/305    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ogino, S.
Right arrow Articles by Fuchs, C. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ogino, S.
Right arrow Articles by Fuchs, C. S.
Journal of Molecular Diagnostics 2007, Vol. 9, No. 3
Copyright © 2007 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2007.060170

Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample

Shuji Ogino*{dagger}{ddagger}, Takako Kawasaki{dagger}, Gregory J. Kirkner§, Peter Kraft, Massimo Loda*{dagger}{ddagger} and Charles S. Fuchs{dagger}{ddagger}§

From the Departments of Pathology * and Medicine, § Brigham and Women’s Hospital, Boston; the Department of Medical Oncology, {dagger} Dana-Farber Cancer Institute, Boston; Harvard Medical School, {ddagger} Boston; and the Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts

The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at ≥6/8 or ≥5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated ≥85% sensitivity and ≥80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high.




This article has been cited by other articles:


Home page
J. Mol. Diagn.Home page
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]


Home page
Clin. Cancer Res.Home page
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]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
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]


Home page
Clin. Cancer Res.Home page
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]


Home page
JCOHome page
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]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
S. N. Vasilatos, G. Broadwater, W. T. Barry, J. C. Baker Jr., S. Lem, E. C. Dietze, G. R. Bean, A. D. Bryson, P. G. Pilie, V. Goldenberg, et al.
CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis
Cancer Epidemiol. Biomarkers Prev., March 1, 2009; 18(3): 901 - 914.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
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]


Home page
Clin. Cancer Res.Home page
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]


Home page
JCOHome page
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]


Home page
JNCI J Natl Cancer InstHome page
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]


Home page
Cancer Res.Home page
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]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
E. S. Schernhammer, E. Giovannuccci, C. S. Fuchs, and S. Ogino
A Prospective Study of Dietary Folate and Vitamin B and Colon Cancer According to Microsatellite Instability and KRAS Mutational Status
Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2895 - 2898.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
J. Geli, N. Kiss, M. Karimi, J.-J. Lee, M. Backdahl, T. J. Ekstrom, and C. Larsson
Global and Regional CpG Methylation in Pheochromocytomas and Abdominal Paragangliomas: Association to Malignant Behavior
Clin. Cancer Res., May 1, 2008; 14(9): 2551 - 2559.
[Abstract] [Full Text] [PDF]


Home page
J. Mol. Diagn.Home page
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]


Home page
GutHome page
W. M Grady
CIMP and colon cancer gets more complicated
Gut, November 1, 2007; 56(11): 1498 - 1500.
[Full Text] [PDF]


Home page
GutHome page
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]


Home page
CarcinogenesisHome page
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]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society for Investigative Pathology and the Association for Molecular Pathology.