title: Molecular, histopathological, and genomic variants of glioblastoma.
abstract: Glioblastoma (GBM), the most common primary brain tumor, has a poor median prognosis despite modern surgical, chemotherapeutic, and radiation modalities, which have shown little clinical efficacy. Initially categorized by clinicopathological classification into de novo primary GBM and secondary GBM, which arises from lower-grade glioma, genomic studies have elucidated several distinct genotypes. In addition, distinct patterns of dysregulated epidermal growth factor receptor, platelet-derived growth factor receptor, p53, phosphatase and tensin homolog, cell cycle proteins, and isocitrate dehydrogenase 1, as well as loss of heterozygosity in multiple chromosomes complicate the GBM mutational landscape. Even with the many approaches in targeting these mutations, a long-standing clinical cure remains limited because of the tremendous heterogeneity and challenges in developing targeted treatments. Furthermore, this cancer utilizes ingenious approaches to subvert targeted agents and pathological variants of GBM demonstrate distinct molecular signatures, which may impact prognosis. This review discusses the collective understanding of GBM heterogeneity, including molecular, histopathological, and genomic features; why treatments have failed in the past; and how future clinical trials and therapies can be devised.
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karsy
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, NY, 10595, USA.
authors.forename: Tiangui
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, NY, 10595, USA.
authors.forename: George
authors.initials: G
authors.lastname: Kleinman
authors.affiliation: Department of Neurosurgery,University of Ulm, Albert-Einstein-Allee 23, Ulm, D-89081, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Karpel-Massler
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation