Abstract

Colorectal cancer (CRC) is the third most common cause of cancer deaths in men and women in the United States. Hypermethylation at specific CpG islands has been implicated in carcinogenesis. PAX6 (a transcription factor critical for many stages of development) and CDKN2A (a protein coding gene) stand out as potential candidates to study aberrant methylation in CRC. We hypothesized that in CRC, promoter region CpG islands of PAX6 and CDKN2A are hypermethylated. Here, we investigated the methylation status of PAX6 and CDKN2A in CRC and the effects of decitabine treatment. In the present study, we bisulfite converted DNA from HCT-116 cells, designed methylation-sensitive primers, and sequenced the amplified product. We found that decitabine significantly reduces methylation levels at specific CpG sites in the promoter region of CDKN2A. In addition, we demonstrated that decitabine treatment is effective in killing HCT-116 cells using a clonogenic survival assay. In the future, we hope to replicate this data and further our study to establish biomarkers that could serve as potential therapeutic targets in CRC.

Key words

Colorectal cancer, hypermethylation, PAX6, CDKN2A, carcinogenesis, CpG Islands, qPCR

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