Glioblastoma models driven by different mutations converge to the proneural subtype

Francesco Alessandrini, Davide Ceresa, Irene Appolloni, Francesca Pagani, Pietro Luigi Poliani, Daniela Marubbi, Paolo Malatesta

Research output: Contribution to journalArticle

Abstract

The need of reliable syngeneic animal models for gliomas has been addressed in the last decades by reproducing genetic alterations typical of human glioblastoma in the mouse. Since different alterations underlie different molecular glioblastoma subtypes it is commonly expected that tumors induced by specific alterations represent models of the corresponding subtypes. We tested this assumption by a multilevel analysis ranging from a detailed histopathological analysis to a genome-wide expression profiling by microarray and RNA-seq on gliomas induced by two distinct molecular alterations: the overstimulation of the PDGF- and the EGF- pathways. These alterations are landmarks of proneural and classical glioblastoma subtypes respectively. However, our results consistently showed a strong similarity between the two glioma models. The expression profiles of both models converged toward a signature typical of oligodendrocyte progenitor cells, regardless the wide differentiative potential of the cell of origin. A classification based on similarity with human gliomas profiles revealed that both models belong to the proneural subtype. Our results highlight that reproducing a molecular alteration specific of a glioblastoma subtype not necessarily generates a tumor model recapitulating such subtype.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalCancer Letters
Volume469
DOIs
Publication statusPublished - Jan 28 2020

Keywords

  • EGFRvIII
  • Mouse model
  • Oligodendroglial precursor cells
  • PDGF-B
  • RTK

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Alessandrini, F., Ceresa, D., Appolloni, I., Pagani, F., Poliani, P. L., Marubbi, D., & Malatesta, P. (2020). Glioblastoma models driven by different mutations converge to the proneural subtype. Cancer Letters, 469, 447-455. https://doi.org/10.1016/j.canlet.2019.11.010

Glioblastoma models driven by different mutations converge to the proneural subtype. / Alessandrini, Francesco; Ceresa, Davide; Appolloni, Irene; Pagani, Francesca; Poliani, Pietro Luigi; Marubbi, Daniela; Malatesta, Paolo.

In: Cancer Letters, Vol. 469, 28.01.2020, p. 447-455.

Research output: Contribution to journalArticle

Alessandrini, F, Ceresa, D, Appolloni, I, Pagani, F, Poliani, PL, Marubbi, D & Malatesta, P 2020, 'Glioblastoma models driven by different mutations converge to the proneural subtype', Cancer Letters, vol. 469, pp. 447-455. https://doi.org/10.1016/j.canlet.2019.11.010
Alessandrini F, Ceresa D, Appolloni I, Pagani F, Poliani PL, Marubbi D et al. Glioblastoma models driven by different mutations converge to the proneural subtype. Cancer Letters. 2020 Jan 28;469:447-455. https://doi.org/10.1016/j.canlet.2019.11.010
Alessandrini, Francesco ; Ceresa, Davide ; Appolloni, Irene ; Pagani, Francesca ; Poliani, Pietro Luigi ; Marubbi, Daniela ; Malatesta, Paolo. / Glioblastoma models driven by different mutations converge to the proneural subtype. In: Cancer Letters. 2020 ; Vol. 469. pp. 447-455.
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