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Abstract LB-206: Role of Olig2 phosphorylation in pediatric glioma formation

Cancer Research(2014)

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Abstract
Abstract Malignant gliomas are a leading cause of tumor-related mortality in children. Current therapies often have significant adverse effects on brain development and are largely ineffective against aggressive gliomas. The development of rational therapies has been limited by poor information regarding the cell of origin for pediatric glioma and the relevant underlying genetic alterations. Recent findings now reveal that mutations existing in pediatric glioma are different than those seen in adult gliomas. For example, BRAFV600E activating mutations are associated with deletion of the tumor suppressor gene, p16 (Ink4a-Arf), in about 15% of pediatric gliomas. We have generated a faithful genetic mouse model in which there is concomitant activation of BRAFV600E and deletion of Ink4a-Arf in oligodendrocyte progenitor cells (OPCs) leading to the generation of pediatric high-grade glioma. OPCs have been shown to be a potential cell of origin for glioma and expression of Olig2 is found in 100 percent of human pediatric and adult high-grade gliomas. Given that Olig2 is also required for normal myelin development, targeting all Olig2-expressing cells with small molecule inhibitors would likely have detrimental effects. We have recently found that Olig2 protein is present in a phosphorylated form that promotes proliferation of adult glioma cells. In this study, we demonstrate that phospho-Olig2 is expressed in tumorigenic oligodendrocyte progenitor cells and is required for pediatric glioma generation. In addition, we found that phospho-Olig2 and Olig2 interact with different proteins, some of which are feasible drug targets. This study gives insights into new therapies by understanding key protein interactions in normal oligodendrocyte development as well as in tumorigenic oligodendrocyte progenitor cells. Citation Format: Amelie GRIVEAU, An-Chi TIEN, David H. Rowitch. Role of Olig2 phosphorylation in pediatric glioma formation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-206. doi:10.1158/1538-7445.AM2014-LB-206
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Key words
olig2 phosphorylation,pediatric glioma formation
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