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DNA methylation markers in colorectal cancer

Cancer and Metastasis Reviews volume 29, pages 181–206 (2010)Cite this article

Abstract

Colorectal cancer (CRC) arises as a consequence of the accumulation of genetic and epigenetic alterations in colonic epithelial cells during neoplastic transformation. Epigenetic modifications, particularly DNA methylation in selected gene promoters, are recognized as common molecular alterations in human tumors. Substantial efforts have been made to determine the cause and role of aberrant DNA methylation (“epigenomic instability”) in colon carcinogenesis. In the colon, aberrant DNA methylation arises in tumor-adjacent, normal-appearing mucosa. Aberrant methylation also contributes to later stages of colon carcinogenesis through simultaneous methylation in key specific genes that alter specific oncogenic pathways. Hypermethylation of several gene clusters has been termed CpG island methylator phenotype and appears to define a subgroup of colon cancer distinctly characterized by pathological, clinical, and molecular features. DNA methylation of multiple promoters may serve as a biomarker for early detection in stool and blood DNA and as a tool for monitoring patients with CRC. DNA methylation patterns may also be predictors of metastatic or aggressive CRC. Therefore, the aim of this review is to understand DNA methylation as a driving force in colorectal neoplasia and its emerging value as a molecular marker in the clinic.

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Abbreviations

CRC:

colorectal cancer

ESCC:

esophageal squamous cell carcinoma

EAD:

esophageal adenocarcinoma

HNSCC:

head and neck squamous cell carcinoma

CEA:

carcinoembryonic antigen

AFP:

alpha-fetoprotein

CIMP:

CpG island methylator phenotype

CIMP-H:

CIMP-high

CIMP-L:

CIMP-low

CIMP−:

CIMP-negative

CIMP+:

CIMP-positive

MSI:

microsatellite instability

MSS:

microsatellite stable

M-CRN:

multiple colorectal neoplasia

S-CRC:

solitary colorectal cancer

ACF:

aberrant crypt foci

HPP:

hyperplastic polyposis

HP:

hyperplastic polyps

MSP:

methylation-specific PCR

Q-MSP:

quantitative MSP

5-FU:

5-fluorouracil

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Acknowledgement

This study was supported by National Cancer Institute grant (U01-CA84986), Oncomethylome Sciences, and the Flight Attendant Medical Research Institute Young Clinical Scientist Award (M.S. Kim).

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  1. Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II-5M, Baltimore, MD, 21231, USA

    Myoung Sook Kim, Juna Lee & David Sidransky

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  1. Myoung Sook Kim
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  2. Juna Lee
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Correspondence to David Sidransky.

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Kim, M.S., Lee, J. & Sidransky, D. DNA methylation markers in colorectal cancer. Cancer Metastasis Rev 29, 181–206 (2010). https://doi.org/10.1007/s10555-010-9207-6

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Keywords

  • Colon cancer
  • DNA methylation
  • CpG island methylator phenotype
  • Field effect