LGG-13. GANGLIOGLIOMA DEEP TRANSCRIPTOMICS REVEALS A CD34+ PRIMITIVE NEUROECTODERM NEURAL PRECURSOR-LIKE POPULATION

Abstract Gangliogliomas are glioneuronal brain tumors that typically present in childhood or early adulthood. Though most often low-grade, new insights needed to refine tumor classification and identify therapeutic approaches, particularly for unresectable, high-grade, and/or recurrent disease. possess a rare population of immature astrocyte-appearing CD34+ cells. CD34 is expressed neuroectoderm neural precursor cells during embryogenesis. Neural cell expression usually lost prior birth. We hypothesized ganglioglioma represent precursor/stem closely resemble origin. To test this, we evaluated five gangliogliomas with single nucleus RNA-seq, cellular indexing transcriptomes epitopes by sequencing, spatially-resolved RNA-seq. Developmental trajectory analyses uncovered neoplastic hierarchy, CD34+PAX6+SOX2+MSI1+PECAM1-VWF-DCN-COL1A2- being the primordial neuron-like macroglia-like states. Gene regulatory network inference indicated TCF7L2/MEIS1-PAX6 SOX2-mediated transcriptional programming, similar found neuroectodermal/neural development utero. Spatially-resolved transcriptomics revealed precursor-like niche relatively devoid vascular immune used these high-resolution results deconvolute clinically-annotated transcriptomic data, confirming cell-associated gene programs associate compared other tumors. Together, deep approaches characterized hierarchy - identifying tumor-initiating cells, corresponding programs, signaling pathways, associated These findings may facilitate improved classification, diagnosis, investigations.