DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM)

Isabelle Guilleret, Lorena Losi, Sonia T. Chelbi, Sergio Fonda, Stéphanie Bougel, Sara Saponaro, Gaia Gozzi, Loredana Alberti, Richard Braunschweig, Jean Benhattar

Research output: Contribution to journalArticle

Abstract

Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples.

Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume479
Issue number2
DOIs
Publication statusPublished - Oct 14 2016

Keywords

  • DNA methylation
  • Esophageal adenocarcinoma
  • FFPE
  • Profiling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Guilleret, I., Losi, L., Chelbi, S. T., Fonda, S., Bougel, S., Saponaro, S., Gozzi, G., Alberti, L., Braunschweig, R., & Benhattar, J. (2016). DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM). Biochemical and Biophysical Research Communications, 479(2), 231-237. https://doi.org/10.1016/j.bbrc.2016.09.049