Annals of Surgical Oncology

, Volume 18, Issue 8, pp 2338–2347

Epigenomic Analysis of Aberrantly Methylated Genes in Colorectal Cancer Identifies Genes Commonly Affected by Epigenetic Alterations

  • Young-Ho Kim
  • Han Cheol Lee
  • Seon-Young Kim
  • Young Il Yeom
  • Kyung Ju Ryu
  • Byung-Hoon Min
  • Duk-Hwan Kim
  • Hee Jung Son
  • Poong-Lyul Rhee
  • Jae J. Kim
  • Jong Chul Rhee
  • Hee Cheol Kim
  • Ho-Kyung Chun
  • William M. Grady
  • Yong Sung Kim
Translational Research and Biomarkers

DOI: 10.1245/s10434-011-1573-y

Cite this article as:
Kim, YH., Lee, H.C., Kim, SY. et al. Ann Surg Oncol (2011) 18: 2338. doi:10.1245/s10434-011-1573-y

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.

Supplementary material

10434_2011_1573_MOESM1_ESM.doc (76 kb)
Supplementary material 1 (DOC 76 kb)

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Young-Ho Kim
    • 1
  • Han Cheol Lee
    • 2
  • Seon-Young Kim
    • 2
  • Young Il Yeom
    • 2
  • Kyung Ju Ryu
    • 1
  • Byung-Hoon Min
    • 1
  • Duk-Hwan Kim
    • 3
  • Hee Jung Son
    • 1
  • Poong-Lyul Rhee
    • 1
  • Jae J. Kim
    • 1
  • Jong Chul Rhee
    • 1
  • Hee Cheol Kim
    • 4
  • Ho-Kyung Chun
    • 4
  • William M. Grady
    • 5
  • Yong Sung Kim
    • 2
  1. 1.Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Medical Genomic Research CenterKorea Research Institute of Bioscience and BiotechnologyDaejeonKorea
  3. 3.Department of Molecular Cell BiologySungkyunkwan University School of MedicineSuwonKorea
  4. 4.Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  5. 5.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA