In this regard, mutational inactivation of neurofibromatosis-1 (NF1), tuberous sclerosis complex (TSC), and PTEN genes is associated with glioma formation, such that pharmacologic inhibition of mTOR signaling results in attenuated tumor growth.
No germline mutations were found, suggesting that the genetic basis of familial glioma is distinct from that of gliomas occurring in the Li-Fraumeni syndrome, and that inherited mutations of the catalytic domain of neurofibromin do not predispose affected glioma families to these tumors.
Previous studies from our laboratories have used neurofibromatosis-1 (NF1) genetically engineered mouse (GEM) models to understand the spatial restriction of glioma formation to the optic pathway of young children.
Furthermore, NF1 loss was associated with worse overall and disease-specific survival in the lower-grade glioma, but not GBM, Group in The Cancer Genome Atlas cohort.
In this review, we highlight advances in neurofibromatosis type 1 (NF1) genetically engineered mouse brain tumor (glioma) modeling to reveal how cellular and molecular heterogeneity in both the pre-neoplastic/neoplastic and non-neoplastic cellular compartments contribute to gliomagenesis and glioma growth.
We and others have previously shown that brain tumor (glioma) formation in Nf1 genetically engineered mice requires a microenvironment composed of cells heterozygous for a targeted Nf1 mutation.