CB-04EPIGENETIC REGULATION OF GLIOBLASTOMA TUMORIGENICITY: A HYBRID MODEL

摘要: Glioblastoma is one of the most devastating human cancers, with near-uniform fatality within two years diagnosis. Therapeutic failure thought to be related small subpopulations cells that exhibit properties self-renewal and tumorigenicity. Understanding how such attain retain these remains a central question in oncology. One fundamental issue whether tumorigenicity exists static population elite or capacity stochastically acquired. To test models, we assayed vitro tumor sphere formation frequencies vivo growth subclones established glioblastoma lines as well stem cell derived from patients genetically engineered mouse models. Our findings were best described by hybrid model largely deterministic (elite) but opportunities for dynamic (stochastic) interchange between non-tumorigenic tumorigenic states. identify determinants tumorigenicity, performed gene expression profiling subclones. Analysis data suggested property driven variations MYC expression, consistent effects ectopic knockdown. Transitions states associated changes histone modifications at locus, suggesting epigenetic regulation. The role "tumorigenicity gene" fundamentally distinct those previously ascribed oncogenes. suggests need therapeutic strategies disrupt transition