Detection of human neurotropic JC virus DNA sequence and expression of theviral oncogenic protein in pediatric medulloblastomas

Medulloblastoma represents greater than 25% of childhood intracranial neopl asms and is considered a highly malignant tumor. This tumor, which arises p redominantly in the cerebellar vermis, preferentially affects children betw een the ages of 5 and 15. Although the etiology of medulloblastomas in huma ns remains unknown, results from several experiments have indicated that th e human neurotropic JC virus (JCV) is able to induce cerebellar neoplasms i n rodents that exhibit a phenotype similar to that of human medulloblastoma s. JCV is a polyomavirus that is widespread in the human population, with i nfection occurring most frequently in early childhood. In this study, we ha ve examined the possible association of JCV with human medulloblastomas. By using PCR techniques,ve demon strate that 11 of 23 samples of tumor tissue contain DNA sequences corresponding to three different regions of the JCV genome. More importantly we demonstrate the presence of DNA sequences encod ing the N- and C-terminal regions of the JCV oncogenic protein, T antigen, in 11 of 23 samples and the production of T antigen in the nuclei of 4 samp les of tumor tissue. These observations provide evidence for a possible ass ociation of JCV with human medulloblastomas.