Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes

Sheila R. Alcantara Llaguno, Zilai Wang, Daochun Sun, Jian Chen, Jing Xu, Euiseok Kim, Kimmo J. Hatanpaa, Jack M. Raisanen, Dennis K. Burns, Jane E. Johnson, Luis F. Parada

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number2152
Pages (from-to)429-440
Number of pages12
JournalCancer Cell
Volume28
Issue number4
DOIs
StatePublished - Oct 12 2015

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Glioblastoma
Neoplastic Stem Cells
Phenotype
Mutation
Research
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Alcantara Llaguno, S. R., Wang, Z., Sun, D., Chen, J., Xu, J., Kim, E., ... Parada, L. F. (2015). Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes. Cancer Cell, 28(4), 429-440. [2152]. https://doi.org/10.1016/j.ccell.2015.09.007

Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes. / Alcantara Llaguno, Sheila R.; Wang, Zilai; Sun, Daochun; Chen, Jian; Xu, Jing; Kim, Euiseok; Hatanpaa, Kimmo J.; Raisanen, Jack M.; Burns, Dennis K.; Johnson, Jane E.; Parada, Luis F.

In: Cancer Cell, Vol. 28, No. 4, 2152, 12.10.2015, p. 429-440.

Research output: Contribution to journalArticle

Alcantara Llaguno SR, Wang Z, Sun D, Chen J, Xu J, Kim E et al. Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes. Cancer Cell. 2015 Oct 12;28(4):429-440. 2152. https://doi.org/10.1016/j.ccell.2015.09.007
Alcantara Llaguno, Sheila R. ; Wang, Zilai ; Sun, Daochun ; Chen, Jian ; Xu, Jing ; Kim, Euiseok ; Hatanpaa, Kimmo J. ; Raisanen, Jack M. ; Burns, Dennis K. ; Johnson, Jane E. ; Parada, Luis F. / Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes. In: Cancer Cell. 2015 ; Vol. 28, No. 4. pp. 429-440.
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