EPEN-05. TRANSCRIPTIONAL FACTOR-DIRECTED EPIGENETIC REGULATION IN CANCER NEUROSCIENCE OF ZFTA-RELA EPENDYMOMA

Abstract ZFTA-RELA (ZRFUS) ependymoma is a pediatric brain tumor with dismal 10-year progression free survival rates. Prior studies revealed low somatic mutation load in compared to adult glioma, suggesting that developmental mechanisms play key role during disease development. Using human tissues and mouse tumors generated from our autochthonous utero electroporation (IUE) model, we identified cohort of transcription factors (TFs) linked ZRFUS by investigating histone serotonylation changes other epigenetic datasets. We further performed vivo barcode-screening the ETS variant factor 5 (ETV5) sufficient required for progression. To reveal mechanism driven ETV5, applied transcriptomic, epigenetic, proteomic analyses, found ETV5 suppresses neuropeptide Y (NPY) expression binding modulator, chromobox 3 (CBX3). NPY overexpression delays suppressed tumor-driven neuronal activity mice. This study suggests TF can shape tumor-promoting microenvironment through regulation.