508 The Largest Patient-Derived Meningioma Organoid Bank Demonstrates a Robust Model for Transcriptional Analysis of Tumors

INTRODUCTION: Intracranial tumors display both inter- and intra-tumoral heterogeneity, which poses significant challenges in devising effective therapeutic approaches. Among these tumors, meningiomas are the most prevalent within the central nervous system, with an incidence rate of 8.6/100,000people. Presently, in vitro models have limitations in faithfully preserving the cellular diversity found in patient tumors, and they often necessitate prolonged generation times. METHODS: Patient-resected meningioma were dissected into 1mm 2 pieces. An initial histological analysis was conducted to identify and select cell-dense tumor tissue, minimizing the presence of fibrous tissue for subsequent culturing. Tumor pieces were cultured in organoid medium devoid of any serum products or growth factors to maintain the tumor's cellular composition. Immunofluorescent staining was implemented. Bulk RNA-sequencing was carried out to compare the initial tumor tissue with the corresponding organoids at four weeks of culture. RESULTS: In the largest cohort to date of 40 patients, MEN-O were successfully established, representing various anatomical locations and WHO grades. MEN-O exhibited histological and transcriptional features that closely resembled those found in the original patient tumors. Immunofluorescence staining revealing a diverse cellular composition within the MEN-O and maintenance of proliferative rate between the original tumors and the corresponding organoids. CD3+cells were identified within the MEN-O for >2 weeks of culture. Bulk RNA sequencing analysis identified transcriptomic differences between the original tumor tissues and among organoids derived from different tumors. Nonetheless, there were no significant differences observed between the established organoids and their respective original tumor tissues. CONCLUSIONS: Our study successfully established patient-derived MEN-O from a diverse patient cohort establishing the largest MEN-O bank to date, faithfully recapitulating the histological features, cellular composition and transcriptomics of the initial tumor tissue, proving extremely valuable for further analysis of meningiomas.