臺灣博碩士論文加值系統

乳癌是台灣女性常見的癌症之一。正常細胞累積大量的遺傳變異會造成細胞異常增生而形成腫瘤細胞，腫瘤細胞DNA常因細胞自殺或腫瘤壞死，將genomic DNA釋放到血液中。惡性細胞從原發腫瘤溢出，進入循環該處的血液或淋巴系統，將其傳送至體內的其它組織，稱之為「轉移」，而轉移便是造成癌症死亡率增加的主要原因。研究腫瘤細胞的遺傳變異現象，即LOH或MSI和致癌基因的放大，可以用來當作研究腫瘤發生的核酸標誌，希望可以應用在癌症的臨床研究，達到早期偵測的目的。本實驗室之前的研究，找到三個乳癌專一的一級微衛星標誌，包含LPL、TP53、和Ｄ16S413。在本實驗中，我們便利用一級微衛星標誌進行初發型和已轉移乳癌病人血漿DNA中和腫瘤相關的遺傳變異分析，此外也分析正常女性的血漿結果以當作對照組。利用一級微衛星標誌可以在41.2% (14/34)初發型乳癌病人以及在43.9% (18/41)轉移型乳癌病人的血漿中偵測到遺傳變異現象。在統計上轉移型病人與初發型病人的結果無顯著差異(p> 0.05)，在正常人血漿中偵測到14.6%( 6/41)遺傳變異，統計上與初發型病人和轉移型病人的結果在統計上有顯著差異(p=0.009 和 p=0.003)。此外，在轉移型病人血漿中所偵測的基因體不穩定比率跟臨床病理特徵沒有相關性，但是跟不良的預後有顯著相關(p<0.05)。所以一級的微衛星標誌可能是乳癌發生的早期標誌，並且可以預測轉移性乳癌的預後結果。血漿DNA在癌症的研究中，可能是個很好的指標。所以，在另一方面的實驗，我們利用即時定量PCR來進行血漿中MYCN 致癌基因的放大分析，有53.8%的初發型乳癌病人中表現出MYCN基因放大的現象; 在轉移病人中只有12.5%有MYCN 基因放大的現象。但是，在初發型乳癌病人中，有15.4%偵測到MYCN致癌基因缺失現象，而卻有62.5%的轉移型乳癌病人中，偵測到ＭYCN致癌基因缺失。利用統計分析，血漿中MYCN基因放大的現象似乎跟初發型乳癌的發生有關。此外，利用即時定量PCR進行沒有腫瘤疾病的女性、初發型乳癌病人和轉移型乳癌病人血漿中DNA的相對定量，發現沒有腫瘤疾病女性的血漿DNA量在本實驗中明顯的比乳癌病人低。因此，我們推論正常對照組不足的血漿DNA可能會造成其遺傳變異的錯誤解讀，因而造成我們的正常人對照組中，有偵測到高比例的遺傳變異。在本實驗中，我們提供較無侵襲性的方法來檢測乳癌病人血漿DNA的遺傳變異，並且發現血漿中的LOH/MSI和MYCN 基因放大現象的確可以當作預測乳癌發生的早期標誌。期望這樣較無侵襲性的檢測方法在未來可以應用於乳癌的臨床檢驗。

Contents
Chinese Abstract…………………………………………….. ...I
English Abstract………………………………………………..II
Acknowledgement…………………………………………….IV
Introduction …………………………………………………….1
Materials and Methods………………………………………….7
Results…………………………………………………………12
Discussion……………………………………………………..22
References …………………………………………………….33
Table contents…………………………………………………41
Figure contents ……………………………………………….57

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