The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation

Oncotarget
A C SolgaDavid H Gutmann

Abstract

Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma. Similar to the GFAP-Cre transgenic strain previously employed to generate Nf1 optic gliomas, Olig2+ cells also give rise to astrocytes in the murine optic nerve in vivo. However, in contrast to the GFAP-Cre strain where somatic Nf1 inactivation in embryonic neural progenitor/stem cells (Nf1flox/mut; GFAP-Cre mice) results in optic gliomas by 3 months of age in vivo, mice with Nf1 gene inactivation in Olig2+ OPCs (Nf1flox/mut; Olig2-Cre mice) do not form optic gliomas until 6 months of age. These distinct patterns of glioma latency do not reflect differenc...Continue Reading

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Citations

Apr 29, 2018·Journal of Neuroscience Research·Morgan E Freret, David H Gutmann
Apr 10, 2019·Acta Neuropathologica·J Stephen NixFausto J Rodriguez
Jul 10, 2020·Neuro-oncology Advances·Amanda De Andrade Costa, David H Gutmann
Jun 17, 2021·Neuro-oncology·Till MildeDavid H Gutmann

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Methods Mentioned

BETA
xenografts
transgenic

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