MUTATIONS IN THE P53 GENE ARE NOT LIMITED TO CLASSIC HOT-SPOTS AND ARE NOT PREDICTIVE OF P53 PROTEIN EXPRESSION IN HIGH-GRADE NON-HODGKINS-LYMPHOMA

We have investigated the relationship between the p53 genotype and phe notype in a series of 22 high-grade non-Hodgkin's lymphomas (NHLs) in which we sequenced the p53 gene open reading frame (exons 2-11). Immun ostaining for p53 was already available for these cases. Mutations wer e found in 10/22 cases (45%) and 3/10 were in exons 4 or 10 outside th e classic 'hot spot' regions (exons; 5-8). Comparison with immunostain ing indicated that, besides cases with the 'expected' patterns (in whi ch gene mutation and protein detection were either both present or bot h absent) there were also cases in which p53 protein was detected in t he absence of any mutation and those with a mutant gene in which the p rotein was undetectable. These data show that: (1) in high-grade NHLs mutations frequently occur outside the classic hot spot regions and (2 ) staining for p53 is not predictive of the status of the gene, i.e. w hether or not a mutation is present. Therefore in order to document p5 3 involvement in lymphoid tumours it is necessary both to sequence at least the whole translated open reading frame of the gene and to show evidence of protein expression by immunostaining.