https://scholars.lib.ntu.edu.tw/handle/123456789/192069
標題: | 乳癌HMSH2和HMLH1基因突變之研究 Mutations of hMSH2 and hMLH1 in Breast Cancer |
作者: | 張金堅 | 關鍵字: | 乳癌;DNA 錯誤配對修補;hMLH1;hMSH2;突變;breast cancer;DNA mismatch repair;mutation | 公開日期: | 31-七月-1998 | 出版社: | 臺北市:國立臺灣大學醫學院外科 | 摘要: | DNA 錯誤配對修補基因hMSH2 和hMLH1 的缺失曾在大腸癌中被偵測 到,這兩個基因有缺失的病人在遺傳性非息肉大腸癌約占60%,散發性大 腸癌約占15%,並且這些突變並未無好發點。雖然此二基因的突變也曾在 其他癌症,例如卵巢癌及胃癌被偵測到,然而這兩個基因與乳癌的關係並 未被研究過。 乳癌是台灣婦女最常見的惡性腫瘤之一,最近幾年來,罹患乳癌的人數 快速增加,並且患者的年齡有年輕化的趨勢。本計畫的目的即在探討hMSH2 和hMLH1 是否為台灣乳癌癌化的潛在遺傳因子。我們分析了40 位乳癌病 人的檢體,其中有6 位(15%)有hMLH1 的突變,5 位(12.5%)有hMSH2 的突 變,整體的總突變率與散發性大腸癌差不多,與家庭遺傳病史無太大關連, 然而,大多數的突變是在少於50 歲的病人檢體中偵測到(有hMLH1 突變的 6 位中有5 位、有hMSH2 突變的5 位中有3 位少於50 歲)。另外兩位大於 50 歲、有hMSH2 突變者,具有相同的C 到A 的置換,並未改變所攜帶的 蛋白序列,因此可能只是基因的多形性。雖然突變率在年輕與年長兩個族 群中有很明顯的差異(在hMLH1 是19.2%比7.1%,在hMSH2 是11.5%比 0%),然而因樣品數不夠多,並未達生物統計學上的意義。 總合我們的結果,DNA 錯誤配對修補基因hMSH2 和hMLH1 的突變率 在台灣早發的婦女散發性乳癌中偏高(30.7%),突變的位置也無任何好發 點。此二DNA 錯誤配對修補基因的缺失在早發性乳癌可能扮演重要的角 色。 Defects in the DNA mismatch repair genes, hMLH1 and hMSH2, have been detected in colon cancers. Mutations in these two genes combined account for up to 60% in hereditary nonpolyposis colorectal cancer (HNPCC) and 15% in sporadic colon cancers. The mutation spectra show no hot spots. Mutations of these two genes have also been detected in ovarian and gastric cancers. However, the roles of these two genes in breast cancers were not well studied. In Taiwan, breast cancer is one of the most common malignancies in women. Increasing number of cases and early onset have been noted recently. To find the possible genetic factors involved in the carcinogenesis, we screen 40 breast cancer patients for hMLH1 and hMSH2 mutations. Six (15%) and five (12.5%) patients have mutations in hMLH1 and hMSH2 genes, respectively. The overall mutation rates are about the same as those of sporadic colon cancers. There is no association between mutations and family history. However, the majority of mutations were found in the patients younger than 50 years old (five out of six for hMLH1 and three out of five for hMSH2). The two hMSH2 mutations in the older group have the same C to A transversion, which do not change the encoded amino acid (glycine157). Therefore, these two mutation events should be considered as polymorphism. Although there are obvious differences between mutation rates of the young and old groups (19.2% vs. 7.1% for hMLH1, and 11.5% vs. 0% for hMSH2), they are not statistically significant because of low case numbers. In summary, frequencies of mutation in the mismatch repair genes hMLH1 and hMSH2 are high in the Taiwanese sporadic breast cancers with early onset (30.7%) and the mutations have no hot spots. Defects in these two genes may play important roles in tumorigenesis of breast cancers with early onset. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/24380 | 其他識別: | 872314B002136 | Rights: | 國立臺灣大學醫學院外科 |
顯示於: | 醫學系 |
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872314B002136.pdf | 50.04 kB | Adobe PDF | 檢視/開啟 |
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