P53 GENE-MUTATIONS IN HUMAN ASTROCYTIC BRAIN-TUMORS INCLUDING PILOCYTIC ASTROCYTOMAS

Recent molecular biological studies have shown evidence for a distinct pathogenesis of pilocytic astrocytomas based on alterations other tha n mutations of the tumor suppressor gene p53. To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the pr esence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing. Mutations were found in one of seven (14.3%) pilocytic astrocytomas, in one of 18 (5.6%) low grade astrocytomas, and in one of four (25%) anaplastic astrocytomas, but in none of 13 glioblastomas . Sites of missense mutations were in exon 8 (codons 281 and 289), and exon 5 (codon 151). Silent mutation was found in exon 9 (codon 324), which was related to pilocytic astrocytoma. This is, to the authors' k nowledge, the first report that shows a p53 mutation in pilocytic astr ocytomas. However, the P53 mutation was only found in one of seven tum ors of this entity and was a silent mutation, which does not had to ch ange of amino acids. Thus, the significance of this alteration for the development of this special tumor type seems to be low. Nevertheless, it may be a sign Of genetic instability and is thus suggested to be o f certain pathogenetic relevance. The P53 findings concerning the othe r tumors are in accordance with the view of p53 gene mutations to be e arly events in astrocytoma formation. Copyright (C) 1996 by W.B. Saund ers Company