THE P53 GENE AND ITS ROLE IN HUMAN BRAIN-TUMORS

Mutation of the p53 gene is among the most common lesions in a variety of human tumors, including those of the central nervous system. In mo st instances, mutation of one p53 allele is followed by loss of the re maining wild-type allele, resulting in cells with a complete absence o f functional wild-type p53 protein. However, in some situations, such as at initiation of spontaneously arising gliomas or as the germline c onfiguration of patients with the Li-Fraumeni syndrome, cells clearly carry both wildtype and mutant p53 alleles. These observations lead to the hypothesis that p53 mutations can give rise to loss of tumor supp ressor functions as well as to gain of oncogenic transformation capabi lities. In this review, we define the types of mutations that occur in the p53 gene in various glial tumors, contrast that with the spectra described in other human tumor types, and discuss the biochemistry and physiology of the p53 protein and its ability to regulate and be regu lated by other gene products. We use this information to propose roles for p53 in the initiation and progression of human gliomas. (C) 1995 Wiley-Liss, Inc.