title: Advances in the molecular genetics of gliomas - implications for classification and therapy.
abstract: Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.
authors.affiliation: Department of Neuropathology, Heinrich Heine University Düsseldorf, Moorenstrasse. 5, D-40225 Düsseldorf, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, partner site Essen/Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.affiliation: Department of Neurology and Brain Tumour Centre, Cancer Centre Zürich, University Hospital and University of Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, Switzerland.|Human Biology Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, C3-111, PO Box 19024, Seattle, Washington 98109-1024, USA.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Wirsching
authors.affiliation: Department of Neuropathology, Heinrich Heine University Düsseldorf, Moorenstrasse. 5, D-40225 Düsseldorf, Germany.
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Knobbe-Thomsen
authors.affiliation: Department of Neurology and Brain Tumour Centre, Cancer Centre Zürich, University Hospital and University of Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D016543:Central Nervous System Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008967:Molecular Biology; D017410:Practice Guidelines as Topic; D014944:World Health Organization