Genomics：NPM1变异可作为临床癌症诊断指示

科学家们通过对NPM1的基因剂量，表达水平和遗传变异进行了广泛的研究，结果表明，NPM1有可能成为临床癌症诊断的指示。NPM是一个多功能的核仁磷蛋白质，它在细胞增殖和动态平衡中起关键作用，比如核糖体的生物合成，中心粒的复制，细胞循环和细胞分化。

NPM1被认为是癌症遗传学中的一个关键基因，它可以调节ARF-p53肿瘤抑制和细胞凋亡，是第一致癌基因MycD转录靶标，还可以调控p53的稳定性和转录活性。实际上，NPM1存在于正常的细胞中，只有在细胞增殖或是肿瘤发生的情况下，它才会在增殖过程或是致癌的压力下过量表达。芯片分析得出NPM mRNA过量表达同肿瘤高级阶段相关。科学家分析了人膀胱癌NPM1cDNA，发现了在群体中更高的NPM1序列一致性同肿瘤细胞分化，高级肿瘤阶段和复发可能有相关性。NPM1基因变异在群体学意义上将成为一种有价值的，反应同癌症关联的病理生理学工具。

相关论文发表在爱思唯尔期刊《基因组学》（Genomics）上。（科学新闻杂志 周媛媛/编译）

原始出处：

（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 Chen^{a, b}, Ke-Hung Tsui^a, Chiao-Yun Lin^c, Phei-Lang Chang^a, Petrus Tang^c and Benjamin Yat-Ming Yung^{d, ,}

^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.