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Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model.

Borinstein SC, Conerly M, Dzieciatkowski S, Biswas S, Washington MK, Trobridge P, Henikoff S, Grady WM
Mol Carcinog. 2010 49 (1): 94-103

PMID: 19777566 · PMCID: PMC2875385 · DOI:10.1002/mc.20581

Mouse models of intestinal tumors have advanced our understanding of the role of gene mutations in colorectal malignancy. However, the utility of these systems for studying the role of epigenetic alterations in intestinal neoplasms remains to be defined. Consequently, we assessed the role of aberrant DNA methylation in the azoxymethane (AOM) rodent model of colon cancer. AOM induced tumors display global DNA hypomethylation, which is similar to human colorectal cancer. We next assessed the methylation status of a panel of candidate genes previously shown to be aberrantly methylated in human cancer or in mouse models of malignant neoplasms. This analysis revealed different patterns of DNA methylation that were gene specific. Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa. No aberrant methylation of Dapk1 or Mlt1 was detected in the neoplasms, but normal colon mucosa samples displayed methylation of these genes. Finally, p19(Arf), Tslc1, Hltf, and Mlh1 were unmethylated in both the AOM tumors and normal colon mucosa. Thus, aberrant DNA methylation does occur in AOM tumors, although the frequency of aberrantly methylated genes appears to be less common than in human colorectal cancer. Additional studies are necessary to further characterize the patterns of aberrantly methylated genes in AOM tumors.

2009 Wiley-Liss, Inc.

MeSH Terms (29)

Adaptor Proteins, Signal Transducing Animals Apoptosis Regulatory Proteins Azoxymethane Calcium-Calmodulin-Dependent Protein Kinases Cell Adhesion Molecule-1 Cell Adhesion Molecules Colonic Neoplasms Connexins Cyclin-Dependent Kinase Inhibitor p16 Death-Associated Protein Kinases Disease Models, Animal DNA-Binding Proteins DNA Methylation DNA Modification Methylases DNA Repair Enzymes Humans Immunoglobulins Inhibitor of Differentiation Proteins Insulin-Like Growth Factor Binding Protein 3 Intestinal Mucosa Membrane Proteins Mice MutL Protein Homolog 1 Nuclear Proteins Receptors, CXCR4 Repressor Proteins Transcription Factors Tumor Suppressor Proteins

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