title: Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis.
abstract: Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Irina
authors.initials: I
authors.lastname: Vyazunova
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Vilena I
authors.initials: VI
authors.lastname: Maklakova
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Berman
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Ishani
authors.initials: I
authors.lastname: De
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Steffen
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Won
authors.initials: W
authors.lastname: Hong
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Hayley
authors.initials: H
authors.lastname: Lincoln
authors.affiliation: Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: A Sorana
authors.initials: AS
authors.lastname: Morrissy
authors.affiliation: Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Keiko
authors.initials: K
authors.lastname: Akagi
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Brennan
authors.affiliation: Department of Pathology, Division of Neuropathology, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Rodriguez
authors.affiliation: School of Pharmacy and University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Madison, WI, United States of America.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Collier
mesh_terms: D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D017931:DNA Primers; D004251:DNA Transposable Elements; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D051379:Mice; D016133:Polymerase Chain Reaction; D019895:Transposases / Q000235:genetics
chemical_list: D017931:DNA Primers; D004251:DNA Transposable Elements; D005904:Glial Fibrillary Acidic Protein; D019895:Transposases