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Review
. 2013 Apr;25(2):177-83.
doi: 10.1016/j.ceb.2013.01.007. Epub 2013 Feb 8.

Epigenetic regulation of colon cancer and intestinal stem cells

Saher Sue Hammoud  1 , Bradley R Cairns, David A Jones
Affiliations
Review

Epigenetic regulation of colon cancer and intestinal stem cells

Saher Sue Hammoud et al. Curr Opin Cell Biol. 2013 Apr.

Abstract

The importance and role of the cellular epigenome in cell fating and development have been studied for decades. The epigenome encompasses a range of attributes including DNA methylation, histone modifications, and chromatin remodelers; together these components define the cellular transcriptome, identity, and function. The cellular epigenome is dynamic in response to environmental signals, modifiable during normal cell differentiation and is heritable in daughter cells. This plasticity, however, poses a risk for misregulation and may underlie a number of hereditary disorders, development defects, and cancer. Although the first epigenetic change described in cancer was gene hypomethylation [Holliday R, Jeggo PA: Mechanisms for changing gene expression and their possible relationship to carcinogenesis.Cancer Surv 1985, 4:557-581; Feinberg AP, Vogelstein B: Hypomethylation distinguishes genes of some human cancers from their normal counterparts.Nature 1983, 301:89-92], we know that cancers not only display global hypomethylation, but also, site-specific gene hypermethylation in addition to changes in chromatin modifications. Mechanisms explaining the sometimes paradoxical epigenetic changes observed in cancer, their contributions to tumor initiation and progression and how epigenetics relate to genetic events are poorly understood. In this review we will briefly discuss recent findings on the epigenomic states observed in colon cancer, in particular, how perturbations to the genome and epigenome together may contribute to initiation and progression of colon cancer.

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Figures

Figure 1
Figure 1
Model Figure Colon cancer development is a multistep process with known perturbations to the genome and/or epigenome of colonic epithelial or progenitor cells. These perturbations together contribute to initiation and progression of colon cancer. Although, this may be an over simplification of the process, the loss of APC represents a common starting point. Upon loss of APC, the attenuated retionic acid levels and the concomitant upregulation in the DNA demethylases may perturb the differentiated cell fate or may prevent proper colonic progenitor cell differentiation. The upregulation in the DNA demethylases may contribute to the global hypomethylation or facilitate the second hit mutation in a tumor suppressor gene, which provides cancer cells a growth advantage and metastatic potential.
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