Format

Send to

Choose Destination
Cancer Cell. 2015 Oct 12;28(4):429-440. doi: 10.1016/j.ccell.2015.09.007.

Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes.

Author information

1
Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: alcantas@mskcc.org.
2
Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
3
Department of Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
4
Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
5
Department of Developmental Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: paradal@mskcc.org.

Abstract

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.

PMID:
26461091
PMCID:
PMC4607935
DOI:
10.1016/j.ccell.2015.09.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center