title: The emerging role of NG2 in pediatric diffuse intrinsic pontine glioma.
abstract: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2 expression in the majority of DIPG specimens tested and determine that tumors harboring histone 3.3 mutation express the highest NG2 levels. We further demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated in human DIPGs, resulting in the increased expression of NG2. Treatment with 5-Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG primary tumor cells in vitro. NG2 expression is altered (symmetric segregation) in mitotic human DIPG and mouse tumor cells. These mitotic cells co-express oligodendrocyte (Olig2) and astrocyte (glial fibrillary acidic protein, GFAP) markers, indicating lack of terminal differentiation. NG2 knockdown retards cellular migration in vitro, while NG2 expressing neurospheres are highly tumorigenic in vivo, resulting in rapid growth of pontine tumors. NG2 expression is targetable in vivo using miR129-2 indicating a potential avenue for therapeutic interventions. This data implicates NG2 as a molecule of interest in DIPGs especially those with H3.3 mutation.
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, DC, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Yadavilli
authors.affiliation: Department of Neurology and Center for Neuroscience Research, Children's National Health System, Washington, DC, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scafidi
authors.affiliation: Department of Pediatrics and Pathology, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
authors.forename: Oren J
authors.initials: OJ
authors.lastname: Becher
authors.affiliation: Division of Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Saratsis
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, NY, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hiner
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, DC, USA.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Kambhampati
authors.affiliation: Department of Pathology and Lab Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Santi
authors.initials: S
authors.lastname: Mariarita
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.affiliation: Department of Pathology, Children's National Health System, Washington, DC, USA.
authors.forename: Kari-Elise
authors.initials: KE
authors.lastname: Codispoti
authors.affiliation: Division of Neurosurgery, Children's National Health System, Washington, DC, USA.
authors.forename: Suresh N
authors.initials: SN
authors.lastname: Magge
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, DC, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Jyoti K
authors.initials: JK
authors.lastname: Jaiswal
authors.affiliation: Brain Tumor Institute, Center for Neuroscience and Behavioral Medicine, Children's National Health System, Washington, DC, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.affiliation: Research Center for Genetic Medicine, Children's National Health System, Washington, DC, USA.|Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Javad
authors.initials: J
authors.lastname: Nazarian
mesh_terms: D000293:Adolescent; D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000378:metabolism*; D020295:Brain Stem Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D009154:Mutation; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: DIPG; NG2; PDGF; glioma; histone 3