OLIGODENDROCYTE-TYPE-2 ASTROCYTE (O-2A) PROGENITOR CELLS TRANSFORMED WITH C-MYC AND H-RAS FORM HIGH-GRADE GLIOMA AFTER STEREOTACTIC INJECTION INTO THE RAT-BRAIN

The oligodendrocyte-type-2 astrocyte lineage (O-2A) comprises a progen itor cell that is able to differentiate into an oligodendrocyte or ast rocyte irt vitro. The lineage was originally identified in the neonata l rat central nervous system but evidence suggests that the equivalent O-2A lineage also exists in humans, Apart from its putative and widel y studied role in glial repair, this cell type could potentially be in volved in malignant glioma formation. In this study we demonstrate tha t a rat O-2A progenitor cell line carrying the bacterial P-galactosida se reporter gene and transformed with the c-myc and H-ras oncogenes wh ich has lost its differentiation capacity in vitro generates glioma-li ke growth after stereotactic injection into the adult rat brain. Tumou r pathology was similar to human glioblastoma, suggesting that one of the pathways in the generation of human glioblastomas may be the trans formation of adult O-2A progenitor cells. Parallel studies demonstrate d the presence of a DNA-binding protein complex, termed APprog, in a p anel of human glioma cell lines. This protein was initially identified in O-2A;progenitor cells and not their differentiated progeny. These data lead us to propose that APprog could be used as an indicator of t he lineage origin of gliomas.