대장암종에서 암관련 유전자들의 Promoter Methylation과 암종 발생 및 진행과의 관게에 대한 연구 = Promoter Methylation of Cancer Related Genes in Colorectal Carcinogenesis and Progression

다국어 초록 (Multilingual Abstract)

The colorectal corcinoma is one of the most common malignant tumor in Korea and its carcinogenic mechanism has not been elucidated exactly yet. So far, the most common carcinogenic mechanism has been known to be multiple genetic changes. But, the CpG island hypermethylation has been revealed to be one of the most important carcinogenic mechanism second to the genetic changes.
The epigenetic changes characteristically imprint and transfer to the next generation without changes of nucleotide sequences. When the CpG island of promoter or 5'- exon 1 of a specific gene is methylated by DNA methyltrasferases (DNMTs), the gene expression is inhibited.
Carcinogenic mechansisms by promoter methylation has been well known, but the progression of the cancer has not been elucidated yet. The molecular researches on the carcinogenic mechanisms largely depended on the tumor tissue containing various components of cell, due to difficulties in harvesting pure homogeneous tumor cells.
Promoter methylatonof the cancer related genes as APc, hMLH2, p16, DAP-K and MGMT in 50 cases of sporadic colorectal carcinoma was studied.
The pure normal colorectal epithelial cells, and cancer cells from superficial and deep invasive portion were harvested respectively by laser captured microdissection(LCM), and DNA was extracted from them. The promoter methylation was studied by methylation specific poymerase reaction (MSP) after bisulfite modification of the DNA and the expression of the genes by immunohistochemistry.
The results suggests that promoter methylation of the cancer related genes are closely related with the colorectal carcinogenesis and it occurrs from early phase of carcinogenesis, progressing constantly to the late stage. And the promoter methylation of normal epithelial cells increased by age. The p15, known to be the genes related to hematologic malignancy, was closely related to the colorectal carcinoma as well.