Rheumatology 2000; 39: 262-266
© 2000 British Society for Rheumatology
Analysis of p53 tumour suppressor gene somatic mutations in rheumatoid arthritis synovium
1 Institute of Genetic Information, Kyushu University, First Department of Internal Medicine, Faculty of Medicine, Kyushu University and
2 Department of Rheumatology, Clinical Research Center, National Kyushu Medical Center Hospital, Fukuoka, Japan
Objective. In order to study the role of the p53 tumour suppressor gene in the proliferation of rheumatoid arthritis (RA) synovium, we analysed the mutation of p53 in the synovial fibroblast-like type B synoviocyte from RA patients.
Methods. Synovial fibroblast-like type B synoviocytes were prepared from the synovial tissues from nine Japanese patients with RA. The p53 cDNA region from exons 4–11 was screened for mutations by the streamlined mutation detection method in which polymerase chain reaction (PCR) products are post-labelled and are analysed by automated capillary electrophoresis using single-strand conformation polymorphism conditions, followed by direct sequencing of the subclones of the PCR products.
Results. p53 mutation with possible functional alteration was detected in four of the nine RA patients (44.4%). Of a total of 262 p53 cDNA subclones, 10 subclones were carrying 10 p53 mutations, eight of which were associated with amino acid alterations or protein truncation. Of the p53 functional mutations, a substitution of Gly at amino acid residue 245 to Asp (G245D) was identified in two patients in three subclones. G245D was the first mutation that was recurrently identified in different RA individuals. G245D is also one of the relatively common mutations in human cancers.
Conclusions. In some patients with RA, dysfunction of p53 might play a role in the proliferation of the synovial tissue. G245D mutation might especially need further study as it is the first recurrently identified p53 mutation in RA and is also one of the frequently identified mutations in human cancers.
KEY WORDS: p53 tumour suppressor gene, Rheumatoid arthritis, Synoviocytes, G245D.
Correspondence to: K. Hayashi, Institute of Genetic Information, Kyushu University, Fukuoka 812–8582, Japan.
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