| Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus. | |
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MedLine Citation:
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PMID: 19027227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine the relevance of MGMT in Barrett's carcinogenesis, we analyzed promotor hypermethylation and expression of MGMT in Barrett's adenocarcinomas and its paired precursor lesions from 133 patients using a methylation-specific PCR, real-time RT-PCR and immunohistochemistry. Hypermethylation was detected in 78.9% of esophageal adenocarcinomas, in 100% of Barrett's intraepithelial neoplasia, in 88.9% of Barrett's metaplasia, but only in 21.4% of normal esophageal mucosa samples (P<0.001) and correlated significantly with downregulation of MGMT transcripts (P=0.048) and protein expression (P=0.02). Decrease of protein expression was significantly correlated with progressed stage of disease, lymph node invasion and tumor size. We conclude, that aberrant promoter methylation of MGMT is a frequent and early event during tumorigenesis of Barrett's esophagus. High prevalence of MGMT hypermethylation may represent a candidate marker for improved diagnosis and targeted therapy in Barrett's adenocarcinoma. |
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Authors:
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Doerthe Kuester; Wa'el El-Rifai; DunFa Peng; Petra Ruemmele; Ivonne Kroeckel; Brigitte Peters; Christopher A Moskaluk; Manfred Stolte; Klaus Mönkemüller; Frank Meyer; Hans-Ulrich Schulz; Arndt Hartmann; Albert Roessner; Regine Schneider-Stock |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-11-21 |
Journal Detail:
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Title: Cancer letters Volume: 275 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-01-28 Completed Date: 2009-02-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 117-26 Citation Subset: IM |
Affiliation:
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Department of Pathology, Otto-von-Guericke University Magdeburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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genetics,
metabolism* Adult Aged Barrett Esophagus / genetics, metabolism* Carcinoma / genetics, metabolism* DNA Methylation* DNA Modification Methylases / genetics* DNA Repair Enzymes / genetics* Disease Progression Female Gene Silencing* Humans Lymphatic Metastasis Male Metaplasia / genetics, metabolism* Middle Aged Neoplasm Invasiveness Tumor Suppressor Proteins / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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R01CA106176/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tumor Suppressor Proteins; EC 2.1.1.-/DNA Modification Methylases; EC 2.1.1.63/MGMT protein, human; EC 6.5.1.-/DNA Repair Enzymes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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