This project focuses on defining the gene e expression changes during anaplastic progression of isolated glioma tumor progenitor cells, derived and isolated during tumor progression from low grade gliomas through malignant gliomas and glioblastoma. By first isolating defined phenotypes of gliomas-initiating tumor stem cells from different staged tumors, then normalizing the gene expression patterns of these cells to that of normal glial progenitor cells derived from normal tissue, and then comparing those genes differentially expressed by glioma stem cells at each stage of tumor progression, to one another, this project seeks to define those genes dysregulated at all stages of glial tumorigenesis. Our intent in this regard is to identify those transcriptional patterns and predicted signaling pathways involved in glioma growth at all stages of tumor progression, yet not expressed by normal glial progenitors, as a means of identifying molecular targets for drug therapy unlikely to interfere with normal glial function.