PATH-09. SUBTYPE-ASSOCIATED RNA SPLICING CONTROLLED BY GLIOMA DRIVER MUTATIONS REGULATES GLIOMAGENESIS

Abstract Dysregulated RNA alternative splicing (AS) is a hallmark of cancer and has been studied in cancers including glioma. However, whether the dysregulated AS regulating RNA-binding proteins (RBPs) drive gliomagenesis role glioma driver mutations shaping RBP/AS landscape have not studied. Here we describe two AS-defined subtypes that correlate with IDH1 mutation, tumor grade, patient prognosis. Oncogenic isoforms are exclusively associated subtype 2, wild-type gliomas. Modulation representative or subtype-associated RBPs regulate stem-like cell (GSC) tumorgenicity. With human induced pluripotent stem cell-derived model system, demonstrate specific involved AS. Lastly, target sub2-associated RBP anti-sense oligonucleotides to inhibit GSC tumorigenicity. Our data establish relationships between programs identify network as therapeutic vulnerability.