title: The diversity of p53 mutations among human brain tumors and their functional consequences.
abstract: The p53 tumor suppressor is implicated in cell cycle control, DNA repair, replicative senescence and programmed cell death. Inactivation of the p53 contributes to the wide range of human tumors, including glial neoplasms. In this review, we describe the regulation and biochemical properties of p53 protein that may explain its ability to activate various genetic programs underlying cellular responses to stress conditions. The overall spectrum of p53 mutations is rather shared between tumor types indicating that these mutations are not tumor type-specific. However, there is one example of germ-line mutation of p53 gene (the deletion of the codon 236) that is associated with a familiar brain tumor syndrome. We compare the frequency and type of most common mutations among various brain tumours (focusing on glioblastomas) and their consequences on protein functions. Furthermore, we discuss the most promising approaches of potential brain tumor therapy, including an adenovirus-mediated p53 gene transfer. Human glioblastomas are highly sensitive to the effects of p53 activity when the wild-type p53 is introduced ectopically. It suggests that the genetic or pharmacological modulation of the p53 pathway is potentially important strategy in the treatment of human cancers.
authors.affiliation: Laboratory of Transcription Regulation, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Zupanska
authors.forename: Bozena
authors.initials: B
authors.lastname: Kaminska
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D009154:Mutation