title: High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.
abstract: High-grade gliomas are devastating brain tumors associated with a mean survival of <50 weeks. Two of the most common genetic changes observed in these tumors are overexpression/mutation of the epidermal growth factor receptor (EGFR) vIII and loss of PTEN/MMAC1 expression. To determine whether somatically acquired EGFRvIII expression or Pten loss accelerates high-grade glioma development, we used a previously characterized RasB8 glioma-prone mouse strain, in which these specific genetic changes were focally introduced at 4 weeks of age. We show that both postnatal EGFRvIII expression and Pten inactivation in RasB8 mice potentiate high-grade glioma development. Moreover, we observe a concordant loss of Pten and EGFR overexpression in nearly all high-grade gliomas induced by either EGFRvIII introduction or Pten inactivation. This novel preclinical model of high-grade glioma will be useful in evaluating brain tumor therapies targeted to the pathways specifically dysregulated by EGFR expression or Pten loss.
authors.affiliation: Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University Health Network, Toronto, Ontario, Canada.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Wei
authors.forename: Laura
authors.initials: L
authors.lastname: Clarke
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Scheidenhelm
authors.forename: Baoping
authors.initials: B
authors.lastname: Qian
authors.forename: Amanda
authors.initials: A
authors.lastname: Tong
authors.forename: Nesrin
authors.initials: N
authors.lastname: Sabha
authors.forename: Zia
authors.initials: Z
authors.lastname: Karim
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bock
authors.forename: Robert
authors.initials: R
authors.lastname: Reti
authors.forename: Rolf
authors.initials: R
authors.lastname: Swoboda
authors.forename: Enkhtsetseg
authors.initials: E
authors.lastname: Purev
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Lavoie
authors.forename: M Livia
authors.initials: ML
authors.lastname: Bajenaru
authors.forename: Patrick
authors.initials: P
authors.lastname: Shannon
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
authors.forename: David
authors.initials: D
authors.lastname: Kaplan
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002712:Chlorides; D003287:Contrast Media; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C025340:manganese chloride