Abstract
Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. KRAS mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes-miR-200a and let-7c-was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (p=.056) and carcinomas (p=.011) compared with normal tissue. Expressions of miRNA, miR-200a and let-7c were significantly higher in adenomas than normal tissues (p=.008 and p=.045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.
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