Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.
BACKGROUND
The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies.


METHODS
Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis.


RESULTS
We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died.


CONCLUSIONS
Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.
Sarvary
E
E
Semmelweis University, Transplantation and Surgical Clinic, Budapest, Hungary. sarvary@trans.sote.hu
Nagy
P
P
Benjamin
A
A
Szoke
M
M
Remport
A
A
Jansen
J
J
Nemes
B
B
Kobori
L
L
Fehervari
I
I
Sulyok
B
B
Perner
F
F
Varga
M
M
Fazakas
J
J
Lakatos
M
M
Szabo
M
M
Toth
A
A
Járay
J
J
D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D006814:Hungary; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000009:adverse effects*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D015345:Oligonucleotide Probes; D017354:Point Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D017931:DNA Primers; D015345:Oligonucleotide Probes; D016159:Tumor Suppressor Protein p53; D004247:DNA