XLS file - 43K, Summary of all information for DorQ candidates Fold Change: Average fold of normal Olig2 cells vs all tumor samples. P-value: associated limma p-value with and without FDR. Allen ISH: Scoring on Allen Brain Atlas in situ hybridization patterns for a pattern consistent with expression in OPCs. S: Specific, E: Expressed in these cells and others, A: Absent, U: No signal (unscorable), N: Clearly not in OPCs. *Ttr has a pattern suggestive of choroid plexus, consistent with PDGFRA expression in choroid. Ratio Del/Dups - is the ratio of the number of human glioma samples with a deletion to those with duplications, as counted by RAE algorithm (N=216). % of tumors showing a deletion
ARTICLE ABSTRACT
Platelet-derived growth factor receptor alpha–positive oligodendrocyte progenitor cells (OPC) located within the mature central nervous system may remain quiescent, proliferate, or differentiate into oligodendrocytes. Human glioblastoma multiforme tumors often contain rapidly proliferating oligodendrocyte lineage transcription factor 2 (Olig2)-positive cells that resemble OPCs. In this study, we sought to identify candidate pathways that promote OPC differentiation or quiescence rather than proliferation. Gene expression profiling conducted in both normal murine OPCs and highly proliferative Olig2-positive glioma cells identified all the transcripts associated with the highly proliferative state of these cells and showed that among the various cell types found within the brain, Olig2-positive tumor cells are most similar to OPCs. We then subtracted OPC transcripts found in tumor samples from those found in normal brain samples and identified 28 OPC transcripts as candidates for promoting differentiation or quiescence. Systematic analysis of human glioma data revealed that these genes have similar expression profiles in human tumors and were significantly enriched in genomic deletions, suggesting an antiproliferative role. Treatment of primary murine glioblastoma cells with agonists of one candidate gene, Gpr17, resulted in a decreased number of neurospheres. Together, our findings show that comparison of the molecular phenotype of progenitor cells in tumors to the equivalent cells in the normal brain represents a novel approach for the identification of targeted therapies. Cancer Res; 72(18); 4856–68. ©2012 AACR.
