https://scholars.lib.ntu.edu.tw/handle/123456789/188141
標題: | 尋找與人類肝癌有關的抑癌基因之研究 | 作者: | 許金川 | 關鍵字: | hepatocellular carcinoma;micorsatellite analysis;tumor suppressor gene | 公開日期: | 2001 | 出版社: | 臺北市:國立臺灣大學醫學院內科 | 摘要: | 肝細胞癌是全世界最好發的癌症之一,在台灣也是國人癌症死因的第一位,目前真正的 致病機轉仍不清楚。肝癌的發生通常伴隨基因的變化,其中包括致癌基因的活化、或癌抑制基 因的不活化。目前已知有多種人類腫瘤均與癌抑制基因之變異有關。近年來利用染色體中的微 小衛星可以有系統而快速的分析比較每一染色體中基因的變化,更可進一步尋找可能的癌抑制 基因。 我們的研究結果顯示肝癌病患在16q 常有雜合子丟失(LOH)的情形,且細微定位的結果 靠近16q12.1,16q21-22 和16q24.3 。因此表示這些位置可能有癌抑制基因的存在。目前,我們 利用位於16q12.1 的標記(D16S415, D16S419, D16S409, D16S3080 及D16S3034) 開始篩選人 類之細菌人工染色體基因庫(Bacterial Artificial Chromosome Library, BAC Library),並配合表 現序列捕捉系統(exon trapping system)找到表現序列的clones 。總共選殖到15 個可能的表現序 列,與NCBI ( national center for Biotechnology Infornation )的資料庫比對的結果,有二個序列 與最近被發現的KIAA1005 基因序列完全相同。而KIAA 1005 基因在肝癌組織中有同源性丟 失的現象,反轉錄-聚合 連鎖反應(RT-PCR)的結果也顯示mRNA 的表現有差異,因此我們 推測KIAA1005 基因可能是位於16q12.1 附近的假想抑癌基因。 在microarray 的研究方面,則分析了4 對HCC 的病人,找到數十個upregulate 與 downregulate 的基因,將進一步利用定量PCR 來確認結果。 Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and is the leading cause of cancer death in Taiwan. The prognosis of this cancer is extremely poor with survival of only several months after symptoms occurred. Elucidation of the basic genetic changes of HCC is important for the understanding and treatment of this cancer. Cancer is usually accompanied with genetic alternations either through the activation of cellular oncogene or the inactivation of cancer suppressor gene. The recently identified short tandem repeat, the microsatellite, which is widely distributed throughout the whole human genome. Identification of disease genes as well as tumor suppressor genes by microsatellite polymorphism. have been published recently. In this study, we have used 35 microsatellite markers for further fine mapping of LOH. We have confirmed the most frequent regions of LOH for HCC are 16q12.1, 16q22, and 16q24. After analyzing these information, we started to screen the human BAC(Bacterial Artificial chromosome)library by these markers at 16q12.1 and we identified 15 clones. Exon trapping system is used to search the putative exon sequences of BAC genomic clones. Two exon-like sequences are identical to the KIAA1005 gene. Homozygous deletion of KIAA1005 was found in 37%(10 /27) HCCs. These data suggested that the KIAA1005 might be the putative tumor suppressor genes at chromosome 16q12.1. In microarray study, we have assayed 4 pairs of HCCs patients to compare differential gene expression between nontumor part and tumor part. Of the informative genes, 0.3%-0.6% had an expression level in cancer that was 2 fold lower or higher than that in the non-tumor liver samples , designated as differentially expressed genes. The clustering analysis is in process in our lab. As for these up-regulated or down regulated genes, we will apply quantitative PCR to prove these differences in HCCs. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/23526 | 其他識別: | 892323B002011 | Rights: | 國立臺灣大學醫學院內科 |
顯示於: | 醫學系 |
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892323B002011.pdf | 87.31 kB | Adobe PDF | 檢視/開啟 |
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