Alteration of DNA methylation in gastrointestinal carcinogenesis.
DNA methylation is the main epigenetic modification in humans. The methylation of promoter inhibits the transcription in most genes. In normal tissues, isolated CpG dinucleotides in bulk chromatin are often methylated, whereas cytosines in CpG islands are unmethylated. In neoplasms including gastrointestinal cancer, this pattern of methylation is commonly reversed. The alteration of DNA methylation plays a key role in the process of carcinogenesis. The gastrointestinal carcinogenesis is suggested to be associated with the decrease of total genomic DNA methylation; hypomethylation of certain specific oncogenes such as c-myc, c-Ha-ras, c-fos and alpha-fetoprotein; and hypermethylation of the promoter of some tumor suppressor genes containing p16(INK4A), E-cadherin and hMLH1 genes. This review focuses on the analysis methods for methylation, studies for aberrant DNA methylation in gastrointestinal carcinogenesis, and the intervention changing methylation, including the treatment of 5-azacytidine, supplement of folate and gene therapy.
Fang
J Y
JY
Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Shanghai, People's Republic of China. jyfang@public9.sta.net.cn
Xiao
S D
SD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016153:Genes, Suppressor / Q000502:physiology; D006801:Humans; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D009857:Oncogenes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1