Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus

Doerthe Kuester, Wa'el El-Rifai, Dun Fa 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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27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalCancer letters
Volume275
Issue number1
DOIs
StatePublished - Mar 8 2009
Externally publishedYes

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Keywords

  • Barrett's adenocarcinoma
  • Barrett's metaplasia
  • Carcinogenesis
  • Hypermethylation
  • O-methylguanine-DNA methyltransferase (MGMT)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kuester, D., El-Rifai, W., Peng, D. F., Ruemmele, P., Kroeckel, I., Peters, B., Moskaluk, C. A., Stolte, M., Mönkemüller, K., Meyer, F., Schulz, H. U., Hartmann, A., Roessner, A., & Schneider-Stock, R. (2009). Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus. Cancer letters, 275(1), 117-126. https://doi.org/10.1016/j.canlet.2008.10.009