LOW-FREQUENCY OF THE P53 GENE-MUTATIONS IN NEUROBLASTOMA

Background. The p53 gene frequently is affected by point mutations, re arrangements, or deletions that contribute to the genesis or progressi on of a wide variety of human adult solid tumors; however, to the auth ors' knowledge, this gene alteration has not been analyzed in neurobla stoma. Methods. Genomic DNA samples from 20 children with neuroblastom a, including 16 patients with advanced disease, were screened for the presence of mutations in exons 5-9 of the p53 gene, where over 90% of mutations have been reported to be located in human cancer. The screen ing technique employed polymerase chain reaction/single-strand conform ation polymorphism analysis followed by direct DNA sequencing. Results . Heterozygous mutations were detected in 2 of the 20 cases. A silent mutation (T to G transversion) at codon 172 and a missense mutation (G to T transversion) at codon 259 were found in patients with Stage II and Stage IV disease, respectively. Thus, p53 mutations were found to occur in neuroblastoma, but at a low frequency (2 of 20). Conclusions. Our data suggest that in a minority of neuroblastomas, p53 gene mutat ions may play a contributing role in tumorigenesis, but other genes pr esumably play a major role in this tumor.