1. Oncogenic Signaling Is Dominant to Cell of Origin and Dictates Astrocytic or Oligodendroglial Tumor Development from Oligodendrocyte Precursor Cells.
- Author
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Lindberg, Nanna, Yiwen Jiang, Yuan Xie, Bolouri, Hamid, Kastemar, Marianne, Olofsson, Tommie, Holland, Eric C., and Uhrbom, Lene
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CELLULAR signal transduction ,ONCOGENIC proteins ,ASTROCYTES ,OLIGODENDROGLIA ,PROTEIN precursors - Abstract
Stem cells, believed to be the cellular origin of glioma, are able to generate gliomas, according to experimental studies. Here we investigated the potential and circumstances of more differentiated cells to generate glioma development. We and others have shown that oligodendrocyte precursor cells (OPCs) can also be the cell of origin for experimental oligodendroglial tumors. However, the question of whether OPCs have the capacity to initiate astrocytic gliomas remains unanswered. Astrocytic and oligodendroglial tumors represent the two most common groups of glioma and have been considered as distinct disease groups with putatively different origins. Here we show that mouse OPCs can give rise to both types of glioma given the right circumstances. Weanalyzed tumors induced by K-RAS andAKTand compared them to oligodendroglial platelet-derived growth factor B-induced tumors in Ctv-a mice with targeted deletions of Cdkn2a (p16
Ink4a-/- , p19Arf-/- , Cdkn2a-/- ). Our results showed that glioma can originate from OPCs through overexpression of K-RAS and AKT when combined with p19Arf loss, and these tumors displayed an astrocytic histology and high expression of astrocytic markers. We argue that OPCshave the potential to develop both astrocyticandoligodendroglial tumors given loss of p19Arf ,and that oncogenic signaling is dominant to cell of origin in determining glioma phenotype. Our mouse data are supported by the fact that human astrocytoma and oligodendroglioma display a high degree of overlap in global gene expression with no clear distinctions between the two diagnoses. [ABSTRACT FROM AUTHOR]- Published
- 2014
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