Systems biology study of astrocytomagenesis

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Oncogenic events were induced in the adult astrocytes of conditional mutated mice (T, TR, TRP) at 3 months of age. Mutant mice along with tamoxifen-treated controls that did not carry GFAP-CreERTM transgene were sacrificed at different time points after induction and blood serum and brain samples were collected for further analysis. Brain samples were grouped according to their genotype and pathology and used for gene expression microarray analysis (collaboration with L. Hood, Institute for Systems Biology in Seattle, WA) and establishment of cell lines for further functional analysis. The systems approach has been applied to identify key molecular networks involved in astrocytoma initiation and progression. Initial analysis of the microarray data demonstrated dynamic changes of molecular networks during tumor initiation and progression. We initially focused on gene sets which expression gradually increases with tumor grade. These genes were involved in several key molecular networks that mediate DNA replication and repair (e.g. Gins1, Dna2), cell division and chromosome transmission fidelity (e.g. Aspm), regulation of transcription (e.g. Olig2), immune response signaling, stem and progenitor cell biology, and other processes. Selected gene sets will be used for functional analysis in vitro and in vivo. A manuscript describing these studies is in preparation for publication.