@article{5ab010fcafd249eebbfabbe6db619da1,
title = "Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus",
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.",
keywords = "Barrett's adenocarcinoma, Barrett's metaplasia, Carcinogenesis, Hypermethylation, O-methylguanine-DNA methyltransferase (MGMT)",
author = "Doerthe Kuester and Wa'el El-Rifai and Peng, {Dun Fa} and Petra Ruemmele and Ivonne Kroeckel and Brigitte Peters and Moskaluk, {Christopher A.} and Manfred Stolte and Klaus M{\"o}nkem{\"u}ller and Frank Meyer and Schulz, {Hans Ulrich} and Arndt Hartmann and Albert Roessner and Regine Schneider-Stock",
note = "Funding Information: This study was supported in part by financial support for a “Spitzenbonusprojekt” of the Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany (institutional grant to the Department of Pathology, Magdeburg) and by the National Cancer Institute Grant R01CA106176 (WER). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute, Vanderbilt University or University of Magdeburg. The authors thank Dr. Michael Vieth (Department of Pathology, Bayreuth, Germany) for his assistance in verifying the histopathological diagnosis and support in marking the lesions of interest on hematoxylin-eosin-stained sections. The authors are grateful to Simone Staeck, Hiltraud Scharfenort, Nadine Wiest, Claudia Miethke and Carola K{\"u}gler for their skillful technical assistance.",
year = "2009",
month = mar,
day = "8",
doi = "10.1016/j.canlet.2008.10.009",
language = "English (US)",
volume = "275",
pages = "117--126",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",
}
