Kuester, Doerthe and El-Rifai, Wa'el and Peng, Dunfa and Ruemmele, Petra and Kroeckel, Ivonne and Peters, Brigitte and Moskaluk, Christopher A. and Stolte, Manfred and Moenkemueller, Klaus and Meyer, Frank and Schulz, Hans-Ulrich and Hartmann, Arndt and Roessner, Albert and Schneider-Stock, Regine (2009) Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus. CANCER LETTERS, 275 (1). pp. 117-126. ISSN 0304-3835, 1872-7980
Full text not available from this repository. (Request a copy)Abstract
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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA-REPAIR GENE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE PROMOTER; SQUAMOUS-CELL CARCINOMA; HUMAN TUMOR-CELLS; MESSENGER-RNA; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; COLORECTAL TUMORIGENESIS; GASTRIC-CARCINOMA; CPG METHYLATION; LUNG-CANCER; O-6-methylguanine-DNA methyltransferase (MGMT) Hypermethylation; Carcinogenesis; Barrett's metaplasia; Barrett's adenocarcinoma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2020 08:24 |
| Last Modified: | 21 Sep 2020 08:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29284 |
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