Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium AACR Conference on Molecular Diagnostics - 2008
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 5438-5442, November 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Toyota, M.
Right arrow Articles by Issa, J.-P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toyota, M.
Right arrow Articles by Issa, J.-P. J.
[Cancer Research 59, 5438-5442, November 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Aberrant Methylation in Gastric Cancer Associated with the CpG Island Methylator Phenotype1

Minoru Toyota, Nita Ahuja, Hiromu Suzuki, Fumio Itoh, Mutsumi Ohe-Toyota, Kohzoh Imai, Stephen B. Baylin and Jean-Pierre J. Issa2

The Johns Hopkins Oncology Center, Baltimore, Maryland 21231 (M. T., N. A., M. O-T., S. B. B., J-P. J. I.); First Department of Internal Medicine, Sapporo Medical University, Sapporo 060, Japan (H. S., F. I., K. I), and Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 (J-P. J. I.)

Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in cancer. In colorectal cancer, a group of tumors is characterized by a hypermethylator phenotype termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1. To study whether CIMP is present in gastric cancer, the methylation status of five newly cloned CpG islands was examined in 56 gastric cancers using bisulfite-PCR. Simultaneous methylation of three loci or more was observed in 23 (41%) of 56 cancers, which suggests that these tumors have the hypermethylator phenotype CIMP. There was a significant concordance between CIMP and the methylation of known genes including p16, and hMLH1; methylation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P < 0.0001). Methylation of the hMLH1 gene was detected in three of five tumors that showed microsatellite instability, and all three of the cases were CIMP+. The CIMP phenotype is an early event in gastric cancer, being present in the normal tissue adjacent to cancer in 5 of 56 cases. These results suggest that CIMP may be one of the major pathways that contribute to tumorigenesis in gastric cancers.




This article has been cited by other articles:


Home page
 JCOHome page
M. F.G. de Maat, C. J.H. van de Velde, M. P.J. van der Werff, H. Putter, N. Umetani, E. M. Klein-Kranenbarg, R. R. Turner, J. H. J.M. van Krieken, A. Bilchik, R. A.E.M. Tollenaar, et al.
Quantitative Analysis of Methylation of Genomic Loci in Early-Stage Rectal Cancer Predicts Distant Recurrence
J. Clin. Oncol., May 10, 2008; 26(14): 2327 - 2335.
[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
 Endocr Relat CancerHome page
T M Murphy, A S Perry, and M Lawler
The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer
Endocr. Relat. Cancer, March 1, 2008; 15(1): 11 - 25.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
M. Kim, K.-T. Lee, H.-R. Jang, J.-H. Kim, S.-M. Noh, K.-S. Song, J.-S. Cho, H.-Y. Jeong, S.-Y. Kim, H.-S. Yoo, et al.
Epigenetic Down-Regulation and Suppressive Role of DCBLD2 in Gastric Cancer Cell Proliferation and Invasion
Mol. Cancer Res., February 1, 2008; 6(2): 222 - 230.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. F.G. de Maat, C. J.H. van de Velde, N. Umetani, P. de Heer, H. Putter, A. Q. van Hoesel, G. A. Meijer, N. C. van Grieken, P. J.K. Kuppen, A. J. Bilchik, et al.
Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer
J. Clin. Oncol., November 1, 2007; 25(31): 4887 - 4894.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
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]

Home page
 Clin. Cancer Res.Home page
R. Napieralski, K. Ott, M. Kremer, K. Becker, A.-L. Boulesteix, F. Lordick, J. R. Siewert, H. Hofler, and G. Keller
Methylation of Tumor-Related Genes in Neoadjuvant-Treated Gastric Cancer: Relation to Therapy Response and Clinicopathologic and Molecular Features
Clin. Cancer Res., September 1, 2007; 13(17): 5095 - 5102.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. S. Lee, S.-B. Cho, H. E. Lee, M. A Kim, J. H. Kim, D. J. Park, J. H. Kim, H.-K. Yang, B. L. Lee, and W. H. Kim
Protein Expression Profiling and Molecular Classification of Gastric Cancer by the Tissue Array Method
Clin. Cancer Res., July 15, 2007; 13(14): 4154 - 4163.
[Abstract] [Full Text] [PDF]

Home page
 INT J SURG PATHOLHome page
Y.-F. Zhao, Y.-G. Zhang, X.-X. Tian, Juan Du, and Jie Zheng
Aberrant Methylation of Multiple Genes in Gastric Carcinomas
International Journal of Surgical Pathology, July 1, 2007; 15(3): 242 - 251.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Zhang, Z. Li, Y. Cheng, F. Jia, R. Li, M. Wu, K. Li, and L. Wei
CpG Island Methylator Phenotype Association with Elevated Serum {alpha}-Fetoprotein Level in Hepatocellular Carcinoma
Clin. Cancer Res., February 1, 2007; 13(3): 944 - 952.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. J. Marsit, E. A. Houseman, B. C. Christensen, K. Eddy, R. Bueno, D. J. Sugarbaker, H. H. Nelson, M. R. Karagas, and K. T. Kelsey
Examination of a CpG Island Methylator Phenotype and Implications of Methylation Profiles in Solid Tumors
Cancer Res., November 1, 2006; 66(21): 10621 - 10629.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. J. Lacayo, J. F. DiMartino, M. C. Wei, and G. V. Dahl
CpG Island Methylator Phenotype and Childhood Leukemia.
Clin. Cancer Res., August 15, 2006; 12(16): 4787 - 4789.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. H. Tang, D. H. Yang, W. Huang, H. K. Zhou, X. H. Lu, and G. Ye
Hypomethylated P4 Promoter Induces Expression of the Insulin-Like Growth Factor-II Gene in Hepatocellular Carcinoma in a Chinese Population.
Clin. Cancer Res., July 15, 2006; 12(14): 4171 - 4177.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Furlan, I. Carnevali, B. Marcomini, R. Cerutti, E. Dainese, C. Capella, and C. Riva
The High Frequency of De novo Promoter Methylation in Synchronous Primary Endometrial and Ovarian Carcinomas.
Clin. Cancer Res., June 1, 2006; 12(11): 3329 - 3336.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M.-S. Chang, H. Uozaki, J.-M. Chong, T. Ushiku, K. Sakuma, S. Ishikawa, R. Hino, R. R. Barua, Y. Iwasaki, K. Arai, et al.
CpG Island M;ethylation Status in Gastric Carcinoma with and without Infection of Epstein-Barr Virus.
Clin. Cancer Res., May 15, 2006; 12(10): 2995 - 3002.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. W.Y. Chan, S. H. Wei, P. Wen, Z. Wang, D. E. Matei, J. C. Liu, S. Liyanarachchi, R. Brown, K. P. Nephew, P. S. Yan, et al.
Hypermethylation of 18S and 28S Ribosomal DNAs Predicts Progression-Free Survival in Patients with Ovarian Cancer
Clin. Cancer Res., October 15, 2005; 11(20): 7376 - 7383.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. N. Bhalla
Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies
J. Clin. Oncol., June 10, 2005; 23(17): 3971 - 3993.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. M. Stempak, K.-J. Sohn, E.-P. Chiang, B. Shane, and Y.-I. Kim
Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model
Carcinogenesis, May 1, 2005; 26(5): 981 - 990.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Y.N. Ye, W.K.K. Wu, V.Y. Shin, I.C. Bruce, B.C.Y. Wong, and C.H. Cho
Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke
Carcinogenesis, April 1, 2005; 26(4): 827 - 834.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. An, I.-S. Choi, J. C. Yao, S. Worah, K. Xie, P. F. Mansfield, J. A. Ajani, A. Rashid, S. R. Hamilton, and T.-T. Wu
Prognostic Significance of CpG Island Methylator Phenotype and Microsatellite Instability in Gastric Carcinoma
Clin. Cancer Res., January 15, 2005; 11(2): 656 - 663.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
A. H. Lund and M. van Lohuizen
Epigenetics and cancer
Genes & Dev., October 1, 2004; 18(19): 2315 - 2335.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Sun, D. Deng, W.-C. You, H. Bai, L. Zhang, J. Zhou, L. Shen, J.-L. Ma, Y.-Q. Xie, and J.-Y. Li
Methylation of p16 CpG Islands Associated with Malignant Transformation of Gastric Dysplasia in a Population-Based Study
Clin. Cancer Res., August 1, 2004; 10(15): 5087 - 5093.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Satoh, M. Toyota, F. Itoh, Y. Sasaki, H. Suzuki, K. Ogi, T. Kikuchi, H. Mita, T. Yamashita, T. Kojima, et al.
Epigenetic Inactivation of CHFR and Sensitivity to Microtubule Inhibitors in Gastric Cancer
Cancer Res., December 15, 2003; 63(24): 8606 - 8613.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Akiyama, C. Maesawa, S. Ogasawara, M. Terashima, and T. Masuda
Cell-Type-Specific Repression of the Maspin Gene Is Disrupted Frequently by Demethylation at the Promoter Region in Gastric Intestinal Metaplasia and Cancer Cells
Am. J. Pathol., November 1, 2003; 163(5): 1911 - 1919.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. O. O. Chan, S. K. Lam, B. C.-Y. Wong, Y.-L. Kwong, A. Rashid, and G. Tamura
Gene Methylation in Non-Neoplastic Mucosa of Gastric Cancer: Age or Helicobacter pylori Related?
Am. J. Pathol., July 1, 2003; 163(1): 370 - 373.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. P. Whitcomb, D. G. Mutch, T. J. Herzog, J. S. Rader, R. K. Gibb, and P. J. Goodfellow
Frequent HOXA11 and THBS2 Promoter Methylation, and a Methylator Phenotype in Endometrial Adenocarcinoma
Clin. Cancer Res., June 1, 2003; 9(6): 2277 - 2287.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
M. VERMA, B. K. DUNN, S. ROSS, P. JAIN, W. WANG, R. HAYES, and A. UMAR
Early Detection and Risk Assessment Proceedings and Recommendations from the Workshop on Epigenetics in Cancer Prevention
Ann. N.Y. Acad. Sci., March 1, 2003; 983(1): 298 - 319.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Hibi, M. Koike, H. Nakayama, S. Fujitake, Y. Kasai, K. Ito, S. Akiyama, and A. Nakao
A Cancer-prone Case with a Background of Methylation of p16 Tumor Suppressor Gene
Clin. Cancer Res., March 1, 2003; 9(3): 1053 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Kaneda, M. Kaminishi, K. Yanagihara, T. Sugimura, and T. Ushijima
Identification of Silencing of Nine Genes in Human Gastric Cancers
Cancer Res., November 15, 2002; 62(22): 6645 - 6650.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Ogi, M. Toyota, M. Ohe-Toyota, N. Tanaka, M. Noguchi, T. Sonoda, G. Kohama, and T. Tokino
Aberrant Methylation of Multiple Genes and Clinicopathological Features in Oral Squamous Cell Carcinoma
Clin. Cancer Res., October 1, 2002; 8(10): 3164 - 3171.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Lee, W. H. Kim, H.-Y. Jung, M. H. Yang, and G. H. Kang
Aberrant CpG Island Methylation of Multiple Genes in Intrahepatic Cholangiocarcinoma
Am. J. Pathol., September 1, 2002; 161(3): 1015 - 1022.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
J.-P. Issa
Epigenetic Variation and Human Disease
J. Nutr., August 1, 2002; 132(8): 2388S - 2392.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Garcia-Manero, J. Daniel, T. L. Smith, S. M. Kornblau, M.-S. Lee, H. M. Kantarjian, and J.-P. J. Issa
DNA Methylation of Multiple Promoter-associated CpG Islands in Adult Acute Lymphocytic Leukemia
Clin. Cancer Res., July 1, 2002; 8(7): 2217 - 2224.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T.-L. Lee, W. K. Leung, M. W. Y. Chan, E. K. W. Ng, J. H. M. Tong, K.-W. Lo, S. C. S. Chung, J. J. Y. Sung, and K.-F. To
Detection of Gene Promoter Hypermethylation in the Tumor and Serum of Patients with Gastric Carcinoma
Clin. Cancer Res., June 1, 2002; 8(6): 1761 - 1766.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
L. Shen, N. Ahuja, Y. Shen, N. A. Habib, M. Toyota, A. Rashid, and J.-P. J. Issa
DNA Methylation and Environmental Exposures in Human Hepatocellular Carcinoma
J Natl Cancer Inst, May 15, 2002; 94(10): 755 - 761.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. M. Eischen, J. E. Rehg, S. J. Korsmeyer, and J. L. Cleveland
Loss of Bax Alters Tumor Spectrum and Tumor Numbers in ARF-deficient Mice
Cancer Res., April 1, 2002; 62(7): 2184 - 2191.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. H. Kang, S. Lee, W. H. Kim, H. W. Lee, J. C. Kim, M.-G. Rhyu, and J. Y. Ro
Epstein-Barr Virus-Positive Gastric Carcinoma Demonstrates Frequent Aberrant Methylation of Multiple Genes and Constitutes CpG Island Methylator Phenotype-Positive Gastric Carcinoma
Am. J. Pathol., March 1, 2002; 160(3): 787 - 794.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
C. Nguyen, G. Liang, T. T. Nguyen, D. Tsao-Wei, S. Groshen, M. Lubbert, J.-H. Zhou, W. F. Benedict, and P. A. Jones
Susceptibility of Nonpromoter CpG Islands to De Novo Methylation in Normal and Neoplastic Cells
J Natl Cancer Inst, October 3, 2001; 93(19): 1465 - 1472.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-H. Lin, S.-Y. Hsieh, I-S. Sheen, W.-C. Lee, T.-C. Chen, W.-C. Shyu, and Y.-F. Liaw
Genome-wide Hypomethylation in Hepatocellular Carcinogenesis
Cancer Res., May 1, 2001; 61(10): 4238 - 4243.
[Abstract] [Full Text]

Home page
 J. Med. Genet.Home page
J. F Costello and C. Plass
Methylation matters
J. Med. Genet., May 1, 2001; 38(5): 285 - 303.
[Abstract] [Full Text]

Home page
 BloodHome page
M. Toyota, K. J. Kopecky, M.-O. Toyota, K.-W. Jair, C. L. Willman, and J.-P. J. Issa
Methylation profiling in acute myeloid leukemia
Blood, May 1, 2001; 97(9): 2823 - 2829.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Hoon Kang, Y.-H. Shim, H.-Y. Jung, W. Ho Kim, J. Y. Ro, and M.-G. Rhyu
CpG Island Methylation in Premalignant Stages of Gastric Carcinoma
Cancer Res., April 1, 2001; 61(7): 2847 - 2851.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
M. Esteller, P. G. Corn, S. B. Baylin, and J. G. Herman
A Gene Hypermethylation Profile of Human Cancer
Cancer Res., April 1, 2001; 61(8): 3225 - 3229.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
C. A. Eads, R. V. Lord, K. Wickramasinghe, T. I. Long, S. K. Kurumboor, L. Bernstein, J. H. Peters, S. R. DeMeester, T. R. DeMeester, K. A. Skinner, et al.
Epigenetic Patterns in the Progression of Esophageal Adenocarcinoma
Cancer Res., April 1, 2001; 61(8): 3410 - 3418.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
M. Akhtar, Y. Cheng, R. M. Magno, H. Ashktorab, D. T. Smoot, S. J. Meltzer, and K. T. Wilson
Promoter Methylation Regulates Helicobacter pylori-stimulated Cyclooxygenase-2 Expression in Gastric Epithelial Cells
Cancer Res., March 1, 2001; 61(6): 2399 - 2403.
[Abstract] [Full Text]

Home page
 Am. J. Pathol.Home page
G. Strathdee, K. Appleton, M. Illand, D. W. M. Millan, J. Sargent, J. Paul, and R. Brown
Primary Ovarian Carcinomas Display Multiple Methylator Phenotypes Involving Known Tumor Suppressor Genes
Am. J. Pathol., March 1, 2001; 158(3): 1121 - 1127.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Endoh, G. Tamura, Y. Ajioka, H. Watanabe, and T. Motoyama
Frequent Hypermethylation of the hMLH1 Gene Promoter in Differentiated-Type Tumors of the Stomach with the Gastric Foveolar Phenotype
Am. J. Pathol., September 1, 2000; 157(3): 717 - 722.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Suzuki, F. Itoh, M. Toyota, T. Kikuchi, H. Kakiuchi, and K. Imai
Inactivation of the 14-3-3 {{sigma}} Gene Is Associated with 5' CpG Island Hypermethylation in Human Cancers
Cancer Res., August 1, 2000; 60(16): 4353 - 4357.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
T. Ueki, M. Toyota, T. Sohn, C. J. Yeo, J.-P. J. Issa, R. H. Hruban, and M. Goggins
Hypermethylation of Multiple Genes in Pancreatic Adenocarcinoma
Cancer Res., April 1, 2000; 60(7): 1835 - 1839.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Perrais, P. Pigny, M.-P. Buisine, N. Porchet, J.-P. Aubert, and I. Van Seuningen-Lempire
Aberrant Expression of Human Mucin Gene MUC5B in Gastric Carcinoma and Cancer Cells. IDENTIFICATION AND REGULATION OF A DISTAL PROMOTER
J. Biol. Chem., April 27, 2001; 276(18): 15386 - 15396.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.