CSIG-14. THE PDGFRA-REGULATING LNCRNA LINC02283 IS AMPLIFIED IN HIGH-GRADE GLIOMA AND FACILITATES GLIOMAGENESIS

Abstract Long non-coding RNAs (lncRNAs) regulate numerous physiological processes and the etiology of diseases including cancers. However, lncRNA-based therapies are limited because mechanism action many lncRNAs their interaction with binding partners is not completely understood. We have identified LINC02283, a novel oncogenic lncRNA, highly expressed in PDGF Receptor A (PDGFRA)-mutation driven cohort high-grade glioma (HGG) patients which accounts for ~8% cases. LINC02283 gene co-amplifies PDGFRA locus upregulated HGG. expression copy number variation were correlated to that amplification respectively, high levels leads worse survival HGG patients. found transcription essential Glioma Stem cells (GSCs) mutation, its inhibition significantly improves orthotopic xenograft models. Interestingly, overexpression GSCs wild type (wt) - PDGFRA, enhance signaling, increases cell proliferation worsens Inhibition signaling using AG1296, represses endogenous PDGFRA-mutant GSCs, reduces induced PDGFRA-wt suppresses both cellular models Moreover, co-localizes interacts wild-type mutant downstream targets Akt Erk. In feedback regulation, dysregulated induces GSC GBM through activating downstream, Erk pathways, as lncRNA induction function. Thus, blocking LINC02283-PDGFRA could be plausible therapeutic strategy Altogether, our results provide strong evidence drivers activity progression support potential possible targets.