Astrocytes give rise to oligodendrogliomas and astrocytomas after gene transfer of polyoma virus middle T antigen in vivo

The cells of origin for oligodendrogliomas and astrocytomas are not known b ut are presumed to be oligodendrocyte and astrocyte precursors, respectivel y. In this paper we report the generation of mixed gliomas from in vivo tra nsformation of glial fibrillary acidic protein (GFAP)-positive cells (diffe rentiated astrocytes) with polyoma virus middle T antigen (MTA). MTA is a p owerful oncogene that activates a number of signal transduction pathways, i ncluding those proposed to be involved in gliomagenesis, and has been shown to induce tumors in many cell types. We have achieved transfer of MTA expr ession specifically to GFAP(+) cells in vivo using somatic cell, gene trans fer, and find resultant formation of anaplastic gliomas with mixed astrocyt oma and oligodendroglioma morphological features. We conclude that GFAP-exp ressing astrocytes, with appropriate signaling abnormalities, can serve as the cell of origin for oligodendrogliomas, astrocytomas, or mixed gliomas.