title: Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations.
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.
  
  
  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.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. younghokim@skku.edu
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Han Cheol
authors.initials: HC
authors.lastname: Lee
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
authors.forename: Kyung Ju
authors.initials: KJ
authors.lastname: Ryu
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Son
authors.forename: Poong-Lyul
authors.initials: PL
authors.lastname: Rhee
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Rhee
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Ho-Kyung
authors.initials: HK
authors.lastname: Chun
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor