p53 gene mutation and mdm2 gene amplification are uncommon in medulloblastoma.

Loss of heterozygosity is common for the short arm of chromosome 17 in medulloblastomas, and putative medulloblastoma suppressor loci have been localized to 17p13. The colocalization of the p53 tumor suppressor gene to 17p13 raises the possibility that its mutant alleles may play a role in the malignant transformation of "medulloblasts." Mutations and deletions of the p53 gene have been described in many tumor types and in the germline of some individuals with the Li-Fraumeni syndrome, but reports on the status of the p53 and mdm2 (a gene coding for a p53-associated protein reportedly amplified in human sarcomas) genes in medulloblastomas are few and an indication of their roles, if any, in the etiology of this important childhood tumor has yet to emerge. Here we have analyzed polymerase chain reaction-amplified products of exons 4-9 (95% of reported p53 mutations occur within this region) of the p53 gene in 9 medulloblastomas for potential mutations using the technique of single strand conformation polymorphism analysis and DNA sequencing. We found only one mutation, an A-T to T-A transversion involving the second base of codon 285 and resulting in the substitution of valine for glutamic acid, amplification of the mdm2 gene could be detected in zero of eight of these tumors. These findings suggest that genetic events associated with the inactivation of p53 gene occur in only a minor subset of medulloblastomas.