The p53 Gene and Protein in Human Brain Tumors

Abstract

p53 mutation is most likely an integral early step in the formation of a subset of human diffuse, fibrillary astrocytomas, but is not a frequent event in other studied brain tumors. In astrocytomas, p53 mutations are clustered in the conserved regions of the gene and are predominantly single base pair transitions, frequently at CpG dinucleotides. These mutations result in mutant or truncated p53 proteins that lack the transcriptional activating ability to induce G1 arrest, DNA repair, apoptosis or differentiation. On the other hand, some astrocytomas without p53 mutations may accumulate wild-type protein, perhaps as a physiological response to DNA damage or deregulated proliferation in the tumor cells. Finally, while data on the p53 gene and protein studies in human brain tumors are accumulating rapidly, the clinical significance of such data remains unclear.