臺灣博碩士論文加值系統

第一部份：
根據近幾來年針對乳癌的研究，發現BRCA1基因與家族性乳癌的發生有相當密切的關係，而且目前有許多報導是針對不同族群的乳癌病人搜尋BRCA1基因的突變情形，並且試圖建立該地區BRCA1的突變範疇，所以本實驗的目的主要就是想要建立台灣地區乳癌患者BRCA1的突變範疇，實驗方法則是利用定序的方式偵測年輕乳癌、雙側乳癌以及家族性乳癌的患者BRCA1基因的突變情形，每一個定序的片段除了包含exons之外還有鄰近introns的部份區域，結果顯示在56個乳癌病人中發現12個polymorphisms分別位在4個exons和3個introns，另外在一位屬於家族性的乳癌患者中發現一個突變(2845A T)，還有兩個年輕的乳癌患者有LOH的現象，而且也由定序的結果確定台灣地區BRCA1應該由兩個common alleles (a以及b)和一個rare allele (r) 所組成。以卡方考驗分析比較a allele與b allele在乳癌病人和正常人之間分佈的情形，結果顯示台灣地區乳癌的發生與BRCA1 allele的組合模式沒有相關，但是與a allele相連的haplotype可能是影響遺傳性乳癌發生的因素之一，另外由定序的結果則顯示台灣地區乳癌的發生與BRCA1 coding region序列上的變異其相關性並不大。
第二部分：
正常的人類女性細胞都有兩條X染色體，而大部分的女性其中一條X染色體不活化的現象是屬於隨機的方式，不過仍然有少部分的女性屬於非隨機的X染色體不活化現象。目前X染色體非隨機的不活化現象廣泛地被研究，並且指出與X-linked的隱性疾病以及某些癌症的發生有關，所以本實驗的目的主要是探討X染色體非隨機的不活化現象與乳癌發生的相關性以及是否會影響乳癌腫瘤的形成，實驗方法則是根據HUMARA基因是否有甲基化的情形並且計算modified allelic cleavage ratio (CR)以判斷個體X染色體不活化的模式是屬於隨機的還是非隨機的方式，並進一步以卡方考驗分析或費雪正確機率考驗(當期望次數小於5)比較實驗組與對照組是否有顯著差異，結果顯示在germline DNA所測得的X染色體非隨機的不活化現象與乳癌的發生沒有相關，但是隨著年齡的增長，非隨機的不活化現象有遞增的趨勢。另外，由年齡的因素再進一步分析HUMARA基因alleles的分佈情形以及發生不活化現象的情形，結果發現275bp allele會隨著年齡的增加傾向於不活化的現象；此外，比較乳癌腫瘤組織與鄰近正常組織的X染色體不活化模式，證實X染色體非隨機的不活化現象與乳癌腫瘤的形成有關，以及X染色體上應該有一個或一個以上的腫瘤抑制基因存在，但是非隨機的不活化現象對其他癌症(肝癌、胃癌)腫瘤的形成影響則較小以及可能存在於X染色體上的腫瘤抑制基因對其他癌症而言也不是主要的影響基因。

第一部份：
The BRCA1 gene has been shown to be strongly associated with the occurrence of familial breast cancer. The spectrum of BRCA1 gene mutations in breast cancer patients in various populations has been investigated. In this study, patients in Central Taiwan with breast cancer were screened for BRCA1 mutations by sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. Twelve polymorphisms in 4 exons and 3 introns were found. One mutation was found in one patient with familial breast cancer (2845A T). Two patients showed LOH at the locus of BRCA1. Also found in the Taiwanese population were 2 common alleles and 1 rare allele of BRCA1. These results suggest that the mutation of BRCA1 contributes little to the occurrence of breast cancer in the Taiwanese population.
第二部分：
Normal human female cells contain two X-chromosomes, and one of which is inactivated randomly. However, nonrandom X-chromosome inactivation (NXI) may occur in a subset of females. Recently, a few studies reported that NXI might be a risk factor for the development of some cancers and X-linked diseases. The purpose of this study was to find the relationship between NXI and the development of breast cancers as well as tumorgenesis of breast cancer. X inactivation analysis was performed using HhaI predigestion of DNA followed by PCR of the CAG repeat of the androgen receptor gene (HUMARA), which amplifies the undigested inactive X chromosome only. The Chi-square test or Fisher’s exact probability test (if expected frequency <5) was applied to determine if there was a significant difference in ratios of NXI between experimental and control samples. The results indicated that germline DNA NXI was not associated with the development of breast cancer, and the incidence of NXI was increased with advancing age. However, NXI in breast tissue was found to be associated with the tumorgenesis of breast cancer, whereas it was not highly associated with other cancers (hepatic carcinoma and gastric cancer). The result suggested that there might be a tumor suppressor gene or genes on the X chromosome, which alternation may prone to the development of breast cancer.

第一部份：
(Mutational Screening of Breast Cancer Susceptibility Gene 1from Early-Onset, Bi-lateral, and Familial Breast Cancer Patients in Taiwan)
中文摘要 ----------------------------------------------------1
英文摘要 ----------------------------------------------------2
前言 ----------------------------------------------------3
材料與方法----------------------------------------------------6
實驗結果 ----------------------------------------------------9
討論 ---------------------------------------------------12
參考文獻 ---------------------------------------------------17
圖表 ---------------------------------------------------24
第二部分：
(The Relationship between Nonrandom X-Chromosome Inactivation and Breast Cancer)
中文摘要 -------------------------------------------------- 36
英文摘要 ---------------------------------------------------37
前言 ---------------------------------------------------38
材料與方法---------------------------------------------------44
實驗結果 ---------------------------------------------------47
討論 ---------------------------------------------------52
參考文獻 ---------------------------------------------------64
圖表 ---------------------------------------------------69

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