Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched.

摘要: Brain malignancies represent the most common solid tumors in children, and they are responsible for significant mortality and morbidity. The molecular basis of malignant pediatric brain tumor, medulloblastoma, is poorly understood. Mutations several genes including human homologue Drosophila segment polarity gene, patched (PTCH), the adenomatous polyposis coli gene (APC), β-catenin, p53 have been reported subsets hereditary sporadic medulloblastoma. Inactivation one Ptc allele mice results a 14% incidence medulloblastoma. Here, we report dramatic increase in the incidence (>95%) accelerated development (prior to 12 weeks of age) medulloblastoma heterozygous Ptc that lack p53. The acceleration tumorigenesis in Ptc+/− specific loss of p53, because no change tumor was observed in Ptc+/− carrying mutation in APC (Min+/−) or deficient in p19ARF. Thus, there specific interaction between heterozygosity of Ptc that This may be a consequence increased genomic instability associated with of p53 function enhance rate acquisition of secondary mutations. Ptc+/−p53−/− mice provide useful model investigation molecular bases of medulloblastoma evaluation efficacy therapeutic intervention strategies spontaneously arising endogenous brain tumor.