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ABSTRACT: Background
Determination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC.Materials and methods
We analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa with bead-chip array-based technology.Results
We identified 621 CpG sites located in promoter regions and CpG islands that were greatly hypermethylated in CRC compared to normal mucosa. The genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. Compared to the genome-wide expression array, mRNA expression was more likely to be downregulated in the genes demonstrating promoter hypermethylation, even though this was not statistically significant. We validated ten CpG sites that were hypermethylated (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylation (MAEL, SFT2D3) in CRC compared to the normal mucosa in the array studies using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data.Conclusions
Methylation profiling based on bead-chip arrays is an effective method for screening aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.
SUBMITTER: Kim YH
PROVIDER: S-EPMC3393129 | biostudies-literature | 2011 Aug
REPOSITORIES: biostudies-literature
Kim Young-Ho YH Lee Han Cheol HC Kim Seon-Young SY Yeom Young Il YI Ryu Kyung Ju KJ Min Byung-Hoon BH Kim Duk-Hwan DH Son Hee Jung HJ Rhee Poong-Lyul PL Kim Jae J JJ Rhee Jong Chul JC Kim Hee Cheol HC Chun Ho-Kyung HK Grady William M WM Kim Yong Sung YS
Annals of surgical oncology 20110205 8
<h4>Background</h4>Determination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC.<h4>Materials and methods</h4>We analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa with bead-chip array-based technology.<h4>Results</h4>We identified 62 ...[more]