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Mutant IDH1Promotes Glioma Formation In Vivo
- Source :
- Cell Reports; May 2018, Vol. 23 Issue: 5 p1553-1564, 12p
- Publication Year :
- 2018
-
Abstract
- Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated gene in grade II–III glioma and secondary glioblastoma (GBM). A causal role for IDH1R132Hin gliomagenesis has been proposed, but functional validation in vivohas not been demonstrated. In this study, we assessed the role of IDH1R132Hin glioma development in the context of clinically relevant cooperating genetic alterations in vitroand in vivo. Immortal astrocytes expressing IDH1R132Hexhibited elevated (R)-2-hydroxyglutarate levels, reduced NADPH, increased proliferation, and anchorage-independent growth. Although not sufficient on its own, IDH1R132Hcooperated with PDGFA and loss of Cdkn2a, Atrx, and Ptento promote glioma development in vivo. These tumors resembled proneural human mutant IDH1 GBM genetically, histologically, and functionally. Our findings support the hypothesis that IDH1R132Hpromotes glioma development. This model enhances our understanding of the biology of IDH1R132H-driven gliomas and facilitates testing of therapeutic strategies designed to combat this deadly disease.
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 23
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Cell Reports
- Publication Type :
- Periodical
- Accession number :
- ejs47414865
- Full Text :
- https://doi.org/10.1016/j.celrep.2018.03.133