Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / pathology*
  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Central Nervous System / cytology*
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Mice
  • Mutation
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neurofibromin 1 / genetics
  • PTEN Phosphohydrolase / genetics
  • Tumor Suppressor Protein p53 / genetics


  • Neurofibromin 1
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • Pten protein, mouse

Associated data

  • GEO/GSE57036
  • GEO/GSE57038