SURG-51. A Microneurosurgical Survival Platform for Elucidating Mechanisms of Brain Tumor Recurrence and Metastasis

Abstract BRAIN TUMORS CONTINUE TO EXHIBIT SIGNIFICANT MORBIDITY AND MORTALITY, PARTICULARLY IN CASES OF RECURRENCE AND METASTASIS: Currently there are no in vivo methods to model or interrogate brain tumor recurrence from primary or metastases. Therefore, to elucidate the underlying mechanisms driving these phenomena, we developed a novel recurrent murine model to address this gap in the field. Pediatric medulloblastoma cells were orthotopically implanted into the cerebral cortex or cerebellum in vivo, followed by microneurosurgical tumor resection with murine survival. Comparative transcriptomic analysis, employing RNA sequencing, coupled with Ingenuity Pathway Analysis (IPA), revealed up to 28529 transcriptomic divergence between resected primary and recurrent tumors, indicating dynamic microenvironmental alterations. From this, we identified 2702 common transcriptomics between primary frontal lobe, recurrent frontal lobe, and frontal lobe metastatic tumors. We also identified 3240 common transcriptomics between primary cerebellar, recurrent cerebella, and metastatic cerebellar tumors. IPA demonstrated enrichment of >45 canonical pathways common to both primary and recurrent tumors between the latter transcriptomics. We further identified 18 plasma membrane-specific candidate genes which have significant upregulation in tumor tissue compared to human brain parenchyma. This novel microneurosurgical survival model represents a significant advancement in preclinical brain tumor research, enabling direct interrogation of the molecular and cellular mechanisms driving recurrence and metastasis following surgical resection. By capturing transcriptomic evolution across tumor stages and identifying actionable membrane-associated targets, this platform lays the groundwork for precision immunotherapeutic strategies, including CAR-T cell development, in medulloblastoma and other recurrent brain malignancies.