Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes. Cancer Cell 2015 Oct 12;28(4):429-440
Date
10/16/2015Pubmed ID
26461091Pubmed Central ID
PMC4607935DOI
10.1016/j.ccell.2015.09.007Scopus ID
2-s2.0-84944041780 (requires institutional sign-in at Scopus site) 146 CitationsAbstract
A central question in glioblastoma multiforme (GBM) research is the identity of the tumor-initiating cell, and its contribution to the malignant phenotype and genomic state. We examine the potential of adult lineage-restricted progenitors to induce fully penetrant GBM using CNS progenitor-specific inducible Cre mice to mutate Nf1, Trp53, and Pten. We identify two phenotypically and molecularly distinct GBM subtypes governed by identical driver mutations. We demonstrate that the two subtypes arise from functionally independent pools of adult CNS progenitors. Despite histologic identity as GBM, these tumor types are separable based on the lineage of the tumor-initiating cell. These studies point to the cell of origin as a major determinant of GBM subtype diversity.
Author List
Alcantara Llaguno SR, Wang Z, Sun D, Chen J, Xu J, Kim E, Hatanpaa KJ, Raisanen JM, Burns DK, Johnson JE, Parada LFAuthor
Daochun Sun PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adult Stem CellsAnimals
Brain Neoplasms
Cell Movement
Cell Proliferation
Central Nervous System
Glioblastoma
Humans
Mice
Mutation
Neoplastic Stem Cells
Neurofibromin 1
PTEN Phosphohydrolase
Tumor Suppressor Protein p53
