MUTATION OF THE P53-GENE IN NEUROBLASTOMA AND ITS RELATIONSHIP WITH N-MYC AMPLIFICATION

Mutation of the p53 tumor suppressor gene frequently occurs in a varie ty of tumors including lung, breast, gastrointestinal, and brain, as w ell as lymphomas-leukemias. Neuroblastoma, one of the most common soli d tumors in childhood, often has amplification of the N-myc gene. We e xamined for mutations of the p53 tumor suppressor gene by single-stran d conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assess ed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, tw o mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation w as located in exon 5, and another was in exon 6. N-myc gene was amplif ied in 26% of the samples. No p53 mutations were found in neuroblastom a samples with N-myc amplification. In the two individuals, p53 mutati ons appeared as their disease became more progressive. The neurofibrom atosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spo t of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were un able to detect an abnormality in this region of NF1 in 50 samples of n euroblastoma. The data suggest that p53 mutations occasionally are ass ociated with progression of neuroblastomas, and tumorigenetic influenc es of mutant p53 may differ from those of N-myc.