Origin of the medulloblastoma experimentally induced by human polyomavirus JC.

The origin of the medulloblastoma induced by JC virus (JCV) in golden hamsters was investigated by the in situ hybridization method. After inoculation of JCV into newborn hamsters, a few migrating cells in the cerebellar molecular layer as well as several cells in the internal granular layer hybridized with an antisense mRNA probe of JCV T-antigen on the 10th day. The number of cells positive for this probe decreased on the 15th and 20th days. Moreover, an incipient medulloblastoma consisting of many cells positive for T-antigen mRNA was noticed in the cerebellar internal granular layer 30 days after inoculation. About 6 months post inoculation, 95% of the animals had succumbed to medulloblastoma. Therefore, the origin of the medulloblastoma seemed to be the cells in the cerebellar external granular layer that were infected by JCV, that migrated normally through the molecular layer to the internal granular layer, and that began to proliferate to become medulloblastoma. When 5-day-old hamsters were inoculated, a few cells positive for T-antigen mRNA were detected in the cerebellum within a month. In the long-term observation, the ratio of medulloblastoma induction decreased as the age of the animals at inoculation increased. These results support the idea that JCV infects and transforms the cells in the cerebellar external granular layer, because this layer appears only transiently in newborn hamsters.