Glioblastoma models driven by different mutations converge to the proneural subtype. (28th January 2020)

• Record Type: Journal Article
• Authors: Alessandrini, Francesco; Ceresa, Davide; Appolloni, Irene; Pagani, Francesca; Poliani, Pietro Luigi; Marubbi, Daniela; Malatesta, Paolo
• Is Part Of: Cancer letters. Volume 469(2020)
• Page Start: 447
• Page End: 455
• Publication Date: 2020-01-28
• Subjects: Oligodendroglial precursor cells -- RTK -- Mouse model -- PDGF-B -- EGFRvIII; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.11.010
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: Alteration of either PDGF or EGFR pathway induces unexpectedly similar gliomas. Both PDGFB and EGFRvIII induced gliomas share proneural features. Caution is needed inferring glioma subtype from driver mutations in animal models.