人們總是談“癌”色變,，因?yàn)榘┌Y不僅是世界上難以攻克的疾病之一，而且早期癌癥很難被檢測(cè)出來(lái),。從本質(zhì)上來(lái)說(shuō),，癌癥是一種遺傳病。生物技術(shù)的發(fā)展,，比如基因芯片讓研究者能夠在不同的生物儀器和條件的情況下,，進(jìn)行有關(guān)癌癥的、多基因的高通量比較,。成千上萬(wàn)的基因只有很小的不同,，但是正是這些很小的區(qū)別造成臨床上的差異。
科學(xué)家們通過(guò)對(duì)NPM1的基因劑量,，表達(dá)水平和遺傳變異進(jìn)行了廣泛的研究,，結(jié)果表明，NPM1有可能成為臨床癌癥診斷的指示,。NPM是一個(gè)多功能的核仁磷蛋白質(zhì),，它在細(xì)胞增殖和動(dòng)態(tài)平衡中起關(guān)鍵作用，比如核糖體的生物合成,，中心粒的復(fù)制,，細(xì)胞循環(huán)和細(xì)胞分化,。
NPM1被認(rèn)為是癌癥遺傳學(xué)中的一個(gè)關(guān)鍵基因,，它可以調(diào)節(jié)ARF-p53腫瘤抑制和細(xì)胞凋亡，是第一致癌基因MycD轉(zhuǎn)錄靶標(biāo),，還可以調(diào)控p53的穩(wěn)定性和轉(zhuǎn)錄活性,。實(shí)際上，NPM1存在于正常的細(xì)胞中,，只有在細(xì)胞增殖或是腫瘤發(fā)生的情況下,，它才會(huì)在增殖過(guò)程或是致癌的壓力下過(guò)量表達(dá)。芯片分析得出NPM mRNA過(guò)量表達(dá)同腫瘤高級(jí)階段相關(guān),?？茖W(xué)家分析了人膀胱癌NPM1cDNA，發(fā)現(xiàn)了在群體中更高的NPM1序列一致性同腫瘤細(xì)胞分化,，高級(jí)腫瘤階段和復(fù)發(fā)可能有相關(guān)性,。NPM1基因變異在群體學(xué)意義上將成為一種有價(jià)值的，反應(yīng)同癌癥關(guān)聯(lián)的病理生理學(xué)工具,。
相關(guān)論文發(fā)表在愛思唯爾期刊《基因組學(xué)》（Genomics）上,。（科學(xué)新聞雜志 周媛媛/編譯）
生物谷推薦原始出處：
（Genomics）,，doi:10.1016/j.ygeno.2007.07.006，Chien-Lun Chen,，Benjamin Yat-Ming Yung
Can probability of genetic mutation be an indicator of clinical relevance?
Chien-Lun Chena, b, Ke-Hung Tsuia, Chiao-Yun Linc, Phei-Lang Changa, Petrus Tangc and Benjamin Yat-Ming Yungd, ,
aDepartment of Urology, Chang Gung Memorial Hospital, Chang Gung Bioinformatics Center, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China
bGraduate Institute of Clinical Medical Sciences, College of Medicine, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China
cDepartment of Parasitology, Chang Gung Bioinformatics Center, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China
dDepartment of Pharmacology, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China
Received 30 May 2007; accepted 11 July 2007. Available online 24 October 2007.
Abstract
NPM1 gene mutation evaluated on a population basis is a valuable and realistic tool to reflect the pathophysiological relevance of cancer. In a comparison of the NPM1 cDNA of human bladder cancer with its consensus sequence, we have found that a higher NPM1 sequence identity in a population is consistent with poor tumor differentiation, advanced tumor stage, and likelihood of recurrence. These data imply that “probability” of NPM1 mutation is an indicator of status of malignancy.
