title: Genetics and epigenetics of gliomas.
abstract: Gliomas are the most common primary intrinsic brain tumours. Their classification is based on phenotypic resemblance to normal glial cells (astrocytomas, oligodendrogliomas, mixed oligoastrocytomas) and pathological grading. Whereas this system is clinically relevant and has been the basis for our understanding of gliomas, systematic use of next-generation sequencing has transformed our knowledge of their pathogenesis and has uncovered genetic changes in an unanticipated number of genes and regulatory elements. In the past few years, in-depth analysis of low-grade astrocytomas and glioblastomas in both paediatric and adult populations has clarified our molecular understanding of these diseases, with distinct molecular events occurring in different age groups. In oligodendrogliomas, recent studies have highlighted mutations in candidate tumour suppressor genes located on 1p/19q, chromosome arms frequently deleted in this tumour. In this review, we discuss recent discoveries in the genetics of adult and paediatric gliomas, and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to brain tumour development and will be key for refining classification systems and improving clinical care.
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, and Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Mario Luca
authors.initials: ML
authors.lastname: Suvà
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000367:Age Factors; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics; D044127:Epigenesis, Genetic; D005910:Glioma / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D018832:Molecular Chaperones; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics; D009837:Oligodendroglioma / Q000235:genetics; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein