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DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM)
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Tissue Fixation
Esophageal Neoplasms
Bisulfite sequencing
Biophysics
WIF1
Biology
Adenocarcinoma
FFPE
Biochemistry
Polymerase Chain Reaction
03 medical and health sciences
Fixatives
Cell Line, Tumor
Formaldehyde
Biomarkers, Tumor
Humans
DNA methylation
Esophageal adenocarcinoma
Profiling
Promoter Regions, Genetic
Molecular Biology
Wnt Signaling Pathway
Paraffin Embedding
Wnt signaling pathway
Reproducibility of Results
Promoter
Cell Biology
Methylation
DNA, Neoplasm
Sequence Analysis, DNA
DNA Methylation
Microarray Analysis
Molecular biology
030104 developmental biology
Cancer cell
Illumina Methylation Assay
Feasibility Studies
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....764ace391435795818b914cdb95bce50