Identification of a novel p53 mutation in JCV-induced mouse medulloblastoma

Medulloblastoma, a malignant invasive tumor of the cerebellum, is one of th e most common neoplasms of the nervous system in children. Utilization of t he human neurotropic virus JC virus (JCV) early gene T-antigen allowed the development of a transgenic animal that models human medulloblastoma. Here we describe the characterization of two distinct populations of cells deriv ed from the JCV-induced mouse medulloblastoma. Results from immunohistochem ical and biochemical studies revealed the expression of T-antigen in some b ut not all tumor cells. In T-antigen-producing cells, T-antigen was found i n association with wild-type p53 and pRb, two tumor suppressors that contro l cell growth and differentiation. In cells that lack expression of T-antig en, a novel mutant p53 with a deletion between residues 35 and 123 was dete cted. Morphological differences were observed between the two populations o f cells, though there was no significant difference in their growth rates. However, subcutaneous transplantation of the T-antigen-positive, but not 7- antigen-negative, cells resulted in the development of massive tumors in ex perimental animals. In light of earlier reports on the association of JCV w ith human medulloblastoma, the mouse cell lines described in this study may provide a valuable tool for deciphering the pathways involved in the forma tion and progression of medulloblastoma, (C) 2000 Academic Press.