title: The molecular and cell biology of pediatric low-grade gliomas.
abstract: Pilocytic astrocytoma (PA) is the most common glial cell tumor arising in children. Sporadic cases are associated with KIAA1549:BRAF fusion rearrangements, while 15-20% of children develop PA in the context of the neurofibromatosis 1 (NF1) inherited tumor predisposition syndrome. The unique predilection of these tumors to form within the optic pathway and brainstem (NF1-PA) and cerebellum (sporadic PA) raises the possibility that gliomagenesis requires more than biallelic inactivation of the NF1 tumor suppressor gene or expression of the KIAA1549:BRAF transcript. Several etiologic explanations include differential susceptibilities of preneoplastic neuroglial cell types in different brain regions to these glioma-causing genetic changes, contributions from non-neoplastic cells and signals in the tumor microenvironment, and genomic modifiers that confer glioma risk. As clinically-faithful rodent models of sporadic PA are currently under development, Nf1 genetically-engineered mouse (GEM) models have served as tractable systems to study the role of the cell of origin, deregulated intracellular signaling, non-neoplastic cells in the tumor microenvironment and genomic modifiers in gliomagenesis. In this report, we highlight advances in Nf1-GEM modeling and review new experimental evidence that supports the emerging concept that Nf1- and KIAA1549:BRAF-induced gliomas arise from specific cell types in particular brain locations.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D025542:Neurofibromin 1 / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D025542:Neurofibromin 1; D015514:Oncogene Proteins, Fusion