https://scholars.lib.ntu.edu.tw/handle/123456789/188131
標題: | 尋找位於人類第十六號染色體上可能與肝癌發生有關抑癌基因的研究 | 作者: | 許金川 | 關鍵字: | 肝細胞癌;微小衛星;雜合子丟失;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. KIAA1005 基因目前功能不明,只能就所推測的氨基酸順序所含有的特殊結構來分 析它可能有何種功能,由於KIAA1005 含有Leucine zipper 及C2 domain ,與yeast hypothetical 蛋白及人類desmoplakin 有22%-30%的相同性,所以它可能是transcription factor 或是與desmosomal plaque 有關。KIAA1005 基因的mRNA 表現也非常特殊,似乎 有三種型式,但究竟這兩種型式與原先KIAA 1005 的功能是否相同,需再進一步研究。 而KIAA1005 基因是否真的在肝細胞癌的發生過程扮演重要角色則需要進行更多研究才 能有正確的答案。 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 use microsatellite marker to analyze 88 cases of HCCs, most of them are small in size, in order to study the genetic changes of HCC and to further narrow down the common LOH sites in 16q. 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. The function of KIAA is unknown. From the predicted sequences, we can predict that the gene might be a transcription factor or be correlated with phosphorylation. Furthermore, it seems have different splicing form and play different role in HCC development. However, this need further investigation to elucidate KIAA function. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/23515 | 其他識別: | 892315B002036 | Rights: | 國立臺灣大學醫學院內科 |
顯示於: | 醫學系 |
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892315B002036.pdf | 48.22 kB | Adobe PDF | 檢視/開啟 |
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