نبذة مختصرة : 학위논문 (석사)-- 서울대학교 대학원 : 종양생물학전공, 2017. 2. 강경훈. ; DNA methylation changes occurring in cancer cells are characterized by both promoter CpG island hypermethylation and diffuse genomic hypomethylation. LINE-1 is half-million times repeated in the human genome in an interspersed manner and CpG sites located in 5 untranslated region of LINE-1 are heavily methylated in normal cells and undergo demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. We analyzed 172 cases of intrahepatic cholangiocarcinomas for their methylation status at four CpG sites of LINE-1 using pyrosequencing and correlated LINE-1 methylation level with clinicopathological features. Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites ; LINE-1 methylation level tended to be lower in high grade differentiation, lymphatic emboli, and higher T stage. Lower methylation status of LINE-1 was significantly associated with lower overall survival in patients with intrahepatic cholangiocarcinoma and found to be an independent prognostic parameter. Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. A further study is required to validate our findings. ; Abstract ⅰ Contents ⅱ List of Tables ⅳ List of Figures ⅴ Introduction 1 Materials and Methods 3 DNA extraction and bisulfite modification 3 LINE-1 PCR and Pyrosequencing 4 Statistical analysis 5 Results 6 Demographic and clinicopathological data 6 Relationship between LINE-1 methylation level and clinicopathological features 6 Relationship between tumoral LINE-1 methylation status and overall survival of patients with ICC 10 Discussion 15 References 20 Abstract in Korean 24 ; Master
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