The MDM2 gene amplification database.

The p53 tumor suppressor gene is inactivated in human tumors by several distinct mechanisms. The best characterized inactivation mechanisms are: (i) gene mutation; (ii) p53 protein association with viral proteins; (iii) p53 protein association with the MDM2 cellular oncoprotein. The MDM2 gene has been shown to be abnormally up-regulated in human tumors and tumor cell lines by gene amplification, increased transcript levels and enhanced translation. This communication presents a brief review of the spectrum of MDM2 abnormalities in human tumors and compares the tissue distribution of MDM2 amplification and p53 mutation frequencies. In this study, 3889 samples from tumors or xenografts from 28 tumor types were examined for MDM2 amplification from previously published sources. The overall frequency of MDM2 amplification in these human tumors was 7%. Gene amplification was observed in 19 tumor types, with the highest frequency observed in soft tissue tumors (20%), osteosarcomas (16%) and esophageal carcinomas (13%). Tumors which showed a higher incidence of MDM2 amplification than p53 mutation were soft tissue tumors, testicular germ cell cancers and neuro-blastomas. Data from studies where both MDM2 amplification and p53 mutations were analyzed within the same samples showed that mutations in these two genes do not generally occur within the same tumor. In these studies, 29 out of a total of 33 MDM2 amplification-positive tumors had wild-type p53. We hypothesize that heretofore uncharacterized carcinogens favor MDM2 amplification over p53 mutations in certain tumor types. A database listing the MDM2 gene amplifications is available on the World Wide Web at http://www. infosci.coh.org/mdm2 . Charts of MDM2 amplification frequencies and comparisons with p53 genetic alterations are also available at this Web site.p53抑癌基因可通过多种不同机制在人类肿瘤中发生失活，其中研究最为充分的失活机制包括：(i) 基因突变；(ii) p53蛋白与病毒蛋白结合；(iii) p53蛋白与MDM2细胞癌蛋白结合。已有研究证实，MDM2基因可在人类肿瘤及肿瘤细胞系中通过基因扩增、转录水平升高以及翻译增强等方式出现异常上调。本文简要综述了人类肿瘤中MDM2异常的整体谱况，并对比了MDM2扩增与p53突变频率的组织分布特征。本研究从已发表文献中收集数据，对涵盖28种肿瘤类型的3889份肿瘤或异种移植瘤样本的MDM2扩增情况进行了检测。上述人类肿瘤中MDM2扩增的总体发生率为7%，该基因扩增可在19种肿瘤类型中检出，其中软组织肉瘤、骨肉瘤及食管癌的扩增频率最高，分别为20%、16%和13%。软组织肿瘤、睾丸生殖细胞癌以及神经母细胞瘤的MDM2扩增发生率高于p53突变发生率。针对同时对同一样本中的MDM2扩增与p53突变进行分析的研究数据显示，这两种基因的异常通常不会在同一肿瘤中共存：在这些研究中，33例MDM2扩增阳性的肿瘤中有29例携带野生型p53。我们提出假说：在部分特定肿瘤类型中，此前尚未被鉴定的致癌因素更倾向于诱导MDM2扩增，而非引发p53突变。收录MDM2基因扩增信息的数据库可通过万维网访问，网址为http://www.infosci.coh.org/mdm2，该网站同时提供MDM2扩增频率图表及与p53遗传改变的对比分析结果。