Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. Therefore, there is a critical unmet need to predict therapeutic responses for individual patients. There is 50% of GBM patient has EGFR over-expression and mutation. Because of this reason, there are various EGFRvIII target inhibitor for GBM patient. However, the efficacy of EGFRvIII specific drugs is not good because of autophosphorylation. We found Tra2β, which is pre-mRNA splicing factor, can bind in first intron and there are 9 consensus sequences. Because of EGFRvIII has deletion of second exon, Tra2β can regulate the expression of EGFRvIII. We validated low WTAP expression level in differentiated GBM stem cells, and confirmed the tumorigenic function of Tra2β in GBM cells. Furthermore, we are going to find the mechanism of Tra2β that can regulated by CDC-like kinase. As a result, we connected Tra2β function and EGFR specific drug resistance problem. This study could be helpful on personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs.
Citation Format: Young Taek Oh, Jun Hee Hong, Jong Bae Park. The role of pre-mRNA splicing factor in Glioblastoma Multiforme by regulating EGFRvIII. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A09.