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Mutations in the p53 Tumor Suppressor Gene in Colorectal Cancer in Taiwan

台灣大腸直腸癌p53腫瘤抑制基因的突變

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摘要


抗癌基因p53的突變己被報導盛行於人類的許多腫瘤中,早期偵測抗癌基因p53的突變可提供我們在臨床上處理大腸直腸腫瘤一項有用的資料。在本文中,我們利用聚合脢連鎖反應、單股序列型態多行性(single-strand conformation polymorphism, SSCP)和序列分析(sequence)分析台灣地區大腸直腸腫瘤組織中抗癌基因p53的突變情形。我們利用DneasyTM Tissue Kit萃取台灣南部某教學醫院進行大腸直腸腫瘤切除手術的80位患者組織樣本中的去氧核糖核酸(DNA)並設計引子(primer)分別針對第4、5、6、7和8的位置之表現基因(exon)進行基因放大,接著進行單股序列型態多行性分析和序列分析確定p53基因發生突變的位置。經研究分析後發現有34位患者有不等性的p53基因異常突變,除此之外,亦首次發現密碼子143發生突變與台灣大腸直腸癌亦有關係,另外也發現有兩個插入序列在p53基因exon5的突變裡。在研究中亦發現p53基因的突變與否似乎與腫瘤的轉型與否無關。但卻有五分之二的p53基因突變分佈在台灣大腸直腸腫瘤的患者中,因此認為這p53基因的突變與否或許可以當作大腸直腸腫瘤判斷是否罹患的標準之一。

並列摘要


Mutations in the tumor suppressor gene p53 have been reported as occurring prevalently in a wide range of human tumors. Detection of a mutated p53 is thought to provide useful information for the clinical management of colorectal neoplasm. In this study, we used polymerase chain reaction/ single-strand conformation polymorphism (PCRISSCP) and sequencing analysis to rapidly screen for mutations in p53 in colorectal cancer in Taiwan. Genomic DNA was purified from colorectal cancer specimens obtained from 80 patients at a teaching hospital in southern Taiwan. Primer sets were designed to amplify fragments within exons 4-8 of p53. We found p53 mutations in 38 of 80 patients. This is the first identification of a mutation at codon 143 of p53 in colorectal cancer in Taiwan. In addition, we found two insertions in exon 5 of p53. The p53 mutation rate among colorectal tumors in Taiwan, found in this study, is 43%. The results indicate that p53 mutation is not significantly associated with tumor grade, age, or gender (p > 0.05). We found that two-fifths of colorectal cancer patients in Taiwan have a p53 mutation, which could be used as a marker of colorectal cancer.

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