Abstract
A central question in glioblastoma multiforme (GBM) research is the hierarchy of tumor-initiating cells, and its contribution to the malignant phenotype and genomic make-up of GBM. We examine the potential of adult lineage restricted central nervous system (CNS) progenitors to form malignant gliomas. We show that targeting of Nf1,p53 and Pten mutations in adult CNS progenitors but not stem cells gives rise to fully penetrant GBM. We identify two phenotypically and molecularly distinct GBM subtypes that arise from different adult progenitor lineages. Using multiple inducible cre transgenic lines, we demonstrate that murine GBMs are molecularly separable based on the cell of origin. The oligodendrocyte progenitor cell-derived murine tumors have parallels with a subset of human high-grade gliomas with oligodendrocytic component, tumors that have been ascribed better prognosis compared to classic malignant astrocytomas. These studies indicate that two independent sources of GBM-initiating adult progenitors are susceptible to identical mutations and point to the cell of origin as a major determinant of GBM subtype.
Citation Format: Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo Hatanpaa, Jack Raisanen, Dennis Burns, Jane Johnson, Luis F. Parada. Adult lineage-restricted CNS progenitors specify distinct glioblastoma subtypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-132. doi:10.1158/1538-7445.AM2015-LB-132
- ©2015 American Association for Cancer Research.
Volume 75, Issue 15 Supplement
