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[Cancer Research 60, 5021-5026, September 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Fields of Aberrant CpG Island Hypermethylation in Barrett’s Esophagus and Associated Adenocarcinoma1

Cindy A. Eads, Reginald V. Lord, Soudamini K. Kurumboor, Kumari Wickramasinghe, Margaret L. Skinner, Tiffany I. Long, Jeffrey H. Peters, Tom R. DeMeester, Kathleen D. Danenberg, Peter V. Danenberg, Peter W. Laird2,3 and Kristin A. Skinner2

Departments of Surgery [C. A. E., R. V. L., S. K. K., M. L. S., T. I. L., J. H. P., T. R. D., P. W. L., K. A. S.], Biochemistry and Molecular Biology [C. A. E., T. I. L., K. D. D., P. V. D., P. W. L.], and Pathology [K. W.], University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California 90089-9176

Esophageal adenocarcinoma (EAC) is thought to develop through a multistage process in which Barrett’s metaplasia progresses through low- and high-grade dysplasia to invasive cancer. Transcriptional silencing of tumor suppressor genes by promoter CpG island hypermethylation has been observed in many types of human cancer. Analysis of CpG island hypermethylation in EAC has thus far been limited to the CDKN2A (p16) gene. In this study, we extend the methylation analysis of EAC to include three other genes, APC, CDH1 (E-cadherin), and ESR1 (ER, estrogen receptor {alpha}), in addition to CDKN2A. Molecular analysis can provide insight into the complex relationships between tissues with different histologies in Barrett’s esophagus and associated adenocarcinoma. Therefore, we have mapped the spatial distribution of methylation patterns in six esophagectomy cases in detail. Hypermethylation of the four CpG islands was analyzed by the MethyLight technique in 107 biopsies derived from these six patients for a total of 428 methylation analyses. Our results show that normal esophageal squamous epithelium is unmethylated at all four CpG islands. CDH1 is unmethylated in most other tissue types as well. Hypermethylation of ESR1 is seen at high frequency in inflammatory reflux esophagitis and at all subsequent stages, whereas APC and CDKN2A hypermethylation is found in Barrett’s metaplasia, dysplasia, and EAC. When it occurs, hypermethylation of APC, CDKN2A, and ESR1 is usually found in a large contiguous field, suggesting either a concerted methylation change associated with metaplasia or a clonal expansion of cells with abnormal hypermethylation.




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Home page
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Home page
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Home page
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Home page
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Home page
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Home page
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Mol. Cell. Biol., May 1, 2002; 22(9): 2906 - 2917.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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J. Med. Genet., May 1, 2001; 38(5): 285 - 303.
[Abstract] [Full Text]

Home page
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[Abstract] [Full Text]

Home page
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[Abstract] [Full Text]

Home page
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