STEM-09. NEURAL STEM CELLS OF THE SUBVENTRICULAR ZONE EVOLVE INTO TUMORS AROUND THE RESECTION CAVITY AFTER SURGICAL RESECTION OF GLIOBLASTOMA VIA THE CXCL12/CXCR4 AXIS

Abstract Neural stem cells (NSCs) harboring cancer-driving mutations in the subventricular zone (SVZ) have recently been reported as of origin for human GBM. However, pathological role residual tumor-initiating NSCs (tNSCs) SVZ is undetermined recurrent tumors after surgical removal primary tumor. After resection GBM, most recurrences still appear local around cavity (RC). Accordingly, removal, we hypothesized that tNSCs might be source tumor construction at RC recurrence. Here, examined developing using a mouse model and tissues. First, mutations, including Trp53, Pten, Egfr were introduced to through vivo electroporation, was generated remote cortex resection. We found driver migrated specifically aberrant growth oligodendrocyte-precursor (OPCs). Furthermore, SVZ-originated constituted GBM four weeks post-resection 64% models. Second, CXCR4/CXCL12 axis upregulated migration from formation compared with without RC. Blockage decreased number immigrating OPC lineage switched differentiation tNSC astrocyte lineage. it improved survival rates vivo. Third, validated independent clonal evolution upregulation CXCR4 patient. Taken together, our results reveal tNCSs can re-construct Blocking CXCL12/CXCR4 potential treatment strategy preventing