Most p53 mutations occur in the central part of the p53 gene that codes for the DNA-binding domain. Missense mutations are prevalent. However, 10-25% of all mutations occur outside exons 5-8 and include a prevalence of frameshift, nonsense and splice site mutations. Functional analysis of p53 transactivation ability in yeast (FASAY) was used to screen for p53 mutations in tumors and a mutant p53 protein retaining partial activity was identified. We characterized this somatic p53 mutation in codon 337: transition C-->T, changing codon CGC to TGC and causing substitution of arginine for cysteine in exon 10, which codes for the tetramerization domain of p53. We detected high accumulation of this mutant p53 protein within the tumor tissue and found that it cannot be immunoprecipitated by either a wild-type p53-specific antibody (PAb1620) or by a mutant p53-specific antibody (PAb240). We confirmed the somatic origin of the mutation by analysis of p53 status in peripheral leukocytes.

Masaryk Memorial Cancer Institute Brno Czech Republic

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