An Analysis of Genetic Alterations of the p53 Gene in Human Glioma

Abstract

Restriction fragment length polymorphisms (RFLPs) analysis of human glioma tissue has revealed frequent loss of heterozygosity on the long arm of the chromosome 10 [1] as well as the short arm of the chromosome 17 [2,3]. It has recently been thought that certain tumor suppressor genes are located on chromosomes 10 and 17. The p53 gene is located on 17pl3.1, which is often deleted in various human tumors such as those of colorectal cancer, breast cancer, lung cancer, and osteosarcoma [4]. Detailed study of the p53 gene revealed that the remaining allele contained mutations particularly in the region conserved throughout the species [4]. It is reported that the product of a mutant-type p53 gene has a prolonged half-life and contains a cellular transforming activity. The p53 gene product acts in a dimer and the mutant-type p53 gene product inactivates the wild-type p53 gene product by binding to it [5]. While the mutant-type p53 gene causes cell immortalization in combination with the activated ras gene, the wild-type p53 gene product supresses normal somatic cell transformation. Thus, the genetic alterations of the p53 gene are thought to contribute to the tumorigenetic process in various type of cells, with the p53 gene being a putative tumor suppressor gene. Recent studies revealed that the p53 gene product may be acting as a transcriptional activator for some other genes [6,7]. This fact may well explain the diversity of tumor types which result from mutations in the p53 gene.