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 variety of tumors including lung, breast, gastrointestinal, and brain, as well as lymphomas-leukemias. Neuroblastoma, one of the most common solid tumors in childhood, often has amplification of the N-myc gene. We examined for mutations of the p53 tumor suppressor gene by single-strand conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assessed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, two mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation was located in exon 5, and another was in exon 6. N-myc gene was amplified in 26% of the samples. No p53 mutations were found in neuroblastoma samples with N-myc amplification. In the two individuals, p53 mutations appeared as their disease became more progressive. The neurofibromatosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spot of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were unable to detect an abnormality in this region of NF1 in 50 samples of neuroblastoma. The data suggest that p53 mutations occasionally are associated with progression of neuroblastomas, and tumorigenetic influences of mutant p53 may differ from those of N-myc.