THE MDM2 GENE AMPLIFICATION DATABASE

The p53 tumor suppressor gene is inactivated in human tumors by severa l distinct mechanisms, The best characterized inactivation mechanisms are: (i) gene mutation; (ii) p53 protein association with viral protei ns; (iii) p53 protein association with the MDM2 cellular oncoprotein, The MDM2 gene has been shown to be abnormally up-regulated in human tu mors and tumor cell lines by gene amplification, increased transcript levels and enhanced translation, This communication presents a brief r eview of the spectrum of MDM2 abnormalities in human tumors and compar es the tissue distribution of MDM2 amplification and p53 mutation freq uencies. in this study, 3889 samples from tumors or xenografts from 28 tumor types were examined for MDM2 amplification from previously publ ished sources. The overall frequency of MDM2 amplification in these hu man tumors was 7%, Gene amplification was observed in 19 tumor types, with the highest frequency observed in soft tissue tumors (20%), osteo sarcomas (16%) and esophageal carcinomas (13%), Tumors which showed a higher incidence of MDM2 amplification than p53 mutation were soft tis sue tumors, testicular germ cell cancers and neuroblastomas, Data from studies where both MDM2 amplification and p53 mutations were analyzed within the same samples showed that mutations in these two genes do n ot 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 am plification over p53 mutations in certain tumor types. A database list ing the MDM2 gene amplifications is available on the World Wide Web at http://www.infosci.coh.org/mdm2 . Charts of MDM2 amplification freque ncies and comparisons with p53 genetic alterations are also available at this Web site.