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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

This work was supported by a grant from Samsung Biomedical Research Institute (CB02161).

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Authors and Affiliations

  1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Young-Ho Kim MD, PhD, Kyung Ju Ryu MSc, Byung-Hoon Min MD, PhD, Hee Jung Son MD, PhD, Poong-Lyul Rhee MD, PhD, Jae J. Kim MD, PhD & Jong Chul Rhee MD, PhD

  2. Medical Genomic Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

    Han Cheol Lee PhD, Seon-Young Kim PhD, Young Il Yeom PhD & Yong Sung Kim PhD

  3. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea

    Duk-Hwan Kim MD, PhD

  4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Hee Cheol Kim MD, PhD & Ho-Kyung Chun MD, PhD

  5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    William M. Grady MD, PhD

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  1. Young-Ho Kim MD, PhD
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Correspondence to Young-Ho Kim MD, PhD or Yong Sung Kim PhD.

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Kim, YH., Lee, H.C., Kim, SY. et al. Epigenomic Analysis of Aberrantly Methylated Genes in Colorectal Cancer Identifies Genes Commonly Affected by Epigenetic Alterations. Ann Surg Oncol 18, 2338–2347 (2011). https://doi.org/10.1245/s10434-011-1573-y

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