Genetic perturbations direct the development of distinct brain tumor types from postnatal neural stem/progenitor cells

Primary brain tumors are classified and treated based on their histological features, however the factors which specify these tumor types remain largely unknown. We demonstrate that the over-expression of HRAS (V12) and MYC alone or in combination directs the development of glioma, CNS PNET, and atypical teratoid/rhabdoid (AT/RT)-like tumors from postnatal murine p53-deficient neural stem/progenitor cells. Microarray analyses were performed to investigate the gene expression profile of the tumor cells generated by the different genetic perturbations. Murine brain tumors were generated by overexpressing different oncogenes in cultured neurosphere cells from the postnatal lateral ventricle wall region (LVW) of Trp53-deficient mice. Neurosphere cultures were established from isolated cells of the generated tumors, which still expressed the transgene/fluorescent marker gene cassette. Total RNA was isolated and used for gene expression analyses using the Affymetrix Gene 1.0 ST array platform.