Etmr-22. Identification of 5-Flurouracil as a Selective Therapy in a Novel Ep300::bcor Fusion Glioma Tumor Model

INTRODUCTION BCL6 corepressor gene (BCOR)-altered glioma brain tumors are a newly identified entity which include cases involving a gene fusion with histone acetyltransferase EP300. Treatment strategies for BCOR-fusion gliomas have not yet been established, largely due to their rarity. In this study we utilize a newly established EP300::BCOR fusion cell line to identify effective FDA-approved oncology compounds in vitro. METHODS EP300::BCOR fusion cell line MAF-1211, established from autopsy material, was molecularly defined to confirm the fusion and fidelity with patient samples. The treatment effect of FDA-approved oncology drugs (n=97) in MAF-1211 was compared to other pediatric brain tumor types to identify clinically available compounds with BCOR-fusion glioma selective potency. RESULTS RNAseq analysis of MAF-1211 cell line identified a fusion breakpoint between EP300 exon 31 and BCOR intron 6, which matched both patient presentation and autopsy samples. MAF-1211 also showed molecular fidelity with patient tumors, showing transcriptomic clustering with the patient tumor from which it was established, and matching most strongly with CNS BCOR-altered tumors by DNA methylation classifier analysis. FDA-approved oncology drug screening showed a relatively high sensitivity of MAF-1211 to fluorinated pyrimidines 5-fluorouracil (5-FU), carmofur, and floxuridine compared to other pediatric brain tumor cell lines (HGG, medulloblastoma, ependymoma, ATRT). Discussion: Identification of 5-FU and related drugs identified by our study have the potential to inform design of upcoming clinical studies in BCOR-fusion gliomas. Given the rarity of these tumors it may be more feasible to combine BCOR-fusion gliomas with a potential upcoming clinical trial of 5-FU in posterior fossa A ependymoma.