title: Molecular and Genomic Alterations in Glioblastoma Multiforme.
abstract: In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors.
authors.affiliation: Centre for Neurosciences and Cell Biology, Faculties of Pharmacy and Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ines
authors.initials: I
authors.lastname: Crespo
authors.affiliation: Centre for Neurosciences and Cell Biology, Faculties of Pharmacy and Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Louisa
authors.initials: AL
authors.lastname: Vital
authors.affiliation: Department of Medicine, Centre for Cancer Research (Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer; Centro Superior de Investigaciones Científicas/Universidad de Salamanca; Instituto de Investigación Biomédica de Salamanca), University of Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gonzalez-Tablas
authors.affiliation: Department of Statistics, University of Salamanca, Salamanca, Spain.
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Patino
authors.affiliation: Neurosurgery Service, University Hospital of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Otero
authors.affiliation: Centre for Neurosciences and Cell Biology, Faculties of Pharmacy and Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: María Celeste
authors.initials: MC
authors.lastname: Lopes
authors.affiliation: Centre for Neurosciences and Cell Biology, Faculties of Pharmacy and Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Centre for Neurosciences and Cell Biology, Faculties of Pharmacy and Medicine, University of Coimbra, Coimbra, Portugal; Department of Medicine, Centre for Cancer Research (Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer; Centro Superior de Investigaciones Científicas/Universidad de Salamanca; Instituto de Investigación Biomédica de Salamanca), University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Domingues
authors.affiliation: Department of Medicine, Centre for Cancer Research (Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer; Centro Superior de Investigaciones Científicas/Universidad de Salamanca; Instituto de Investigación Biomédica de Salamanca), University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Department of Medicine, Centre for Cancer Research (Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer; Centro Superior de Investigaciones Científicas/Universidad de Salamanca; Instituto de Investigación Biomédica de Salamanca), University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Institute of Health Science Studies of Castilla and León Research Laboratory, University Hospital of Salamanca, Salamanca, Spain. Electronic address: taberner@usal.es.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D057890:Epigenomics; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009154:Mutation; D015398:Signal Transduction