| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 95 === The process of DNA methylation is a commom existed mechanism in life to modulate epigenetic express. Different degrees of methylation in chromosomes were identified. The phenomenon is explained to modulate the different physiological express by diversity methylation degrees in different kind of species. And each of them has their own dependent physiological express. However, the genetic modultated mechanisms of the methylation are not clearly understood. This study is to analysis the GpG sites of 56 paired non-small lung cancer specimens provided by Taichung Veteran Hospital, and to discover the interaction between the telomerase activation and DNA methylation, and thus, to discover the methylation process in these specimens. We first analysis the methylation situation in telomerase-related gene, like the promoter of hTERT, hTRF1 and hTRF2. The result showed significant relationship between the methylation situation and the activity of the telomerase, and also the tumor stage. When hTERT was meththylated, the telomerase activation was supressed(p=0.038). We also noted that during the process of carcinogenesis, the cells would hypermethylated first (p<0.001) and followed by demethylated(p=0.042). The result collaterally prove the process of methylation in DNA is modulated by two-way mechanism, not one way. Based on the above result, we further separate the specimens into two groups of hypermethylation and hopomethylation of those with telomerase activation and tumor stage. We used DMH microarray technique to detect the overall different degree of methylation of non-small cell lung cancer in 4 cases of each groups. The distribution of the methylation during process of carcinogenesis showed a group of genetic series was demethylated while the cencerization level increased. Thus, we prove the existence of the two-way modulation. In the other way, to discover the sequences that were hypermethylation and the sample’s telomerase activation were inhibited by above genetic sequences. We can survey the relation of methylation patterns of these genetic sequences and activity of telomerase.
Our study successfully explain the two-way modulation of the cells during the process of carcinogesis by analysis the methylation distribution of DNA, which is detected by DMH and MS-PCR method. And the methylation process of DNA in cancer cell was diversity, neither increased nor decreased in one way. We successfully discovered a group of genetic sequence with low grade methylation and activated telomerase by analysis of the above genetic series with cluster analysis. And the result presented in these sequences is compatible with the result by MS-PCR. Our study gained the information of abnormal methylated groups by DMH microarray technique, and further to explore the role of methylation played in cancerization. Finally, to explain the relation of the activity of telomerase and methylation of DNA and we hope to predict and detect the tumor progression by different methylation regions.
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