Mutations in the p53 gene are not limited to classic 'hot spots' and are not predictive of p53 protein expression in high-grade non-Hodgkin's lymphoma.
We have investigated the relationship between the p53 genotype and phenotype 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). Immunostaining for p53 was already available for these cases. Mutations were found in 10/22 cases (45%) and 3/10 were in exons 4 or 10 outside the classic 'hot spot' regions (exons 5-8). Comparison with immunostaining indicated that, besides cases with the 'expected' patterns (in which gene mutation and protein detection were either both present or both absent) there were also cases in which p53 protein was detected in the absence of any mutation and those with a mutant gene in which the protein 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. whether or not a mutation is present. Therefore in order to document p53 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.
Leukaemia Research Fund Immunodiagnostic Unit, University Department of Cellular Science, Oxford.
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S
Kocialkowski
F
F
Pezzella
H
H
Morrison
M
M
Jones
S
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Laha
A L
AL
Harris
D Y
DY
Mason
K C
KC
Gatter
D000595:Amino Acid Sequence; D001483:Base Sequence; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53