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

Publication Type:

Journal Article

Source:

Molecular carcinogenesis, Volume 49, Issue 1, p.94-103 (2010)

Keywords:

2010, Adaptor Proteins, Signal Transducing, Animals, Apoptosis Regulatory Proteins, Azoxymethane, Basic Sciences Division, Calcium-Calmodulin-Dependent Protein Kinases, Center-Authored Paper, Clinical Research Division, Colonic Neoplasms, Comparative Medicine Core Facility, Connexins, Cyclin-Dependent Kinase Inhibitor p16, Disease Models, Animal, DNA Methylation, DNA Modification Methylases, DNA Repair Enzymes, DNA-Binding Proteins, Experimental Histopathology Core Facility, Genomics Core Facility, Humans, Immunoglobulins, Inhibitor of Differentiation Proteins, Insulin-Like Growth Factor Binding Protein 3, Intestinal Mucosa, Membrane Proteins, MICE, Nuclear Proteins, Receptors, CXCR4, Repressor Proteins, Shared Resources, TRANSCRIPTION FACTORS, Tumor Suppressor Proteins

Abstract:

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.