title: Biomarker-driven diagnosis of diffuse gliomas.
abstract: The diffuse gliomas are primary central nervous system tumors that arise most frequently in the cerebral hemispheres of adults. They are currently classified as astrocytomas, oligodendrogliomas or oligoastrocytomas and range in grade from II to IV. Glioblastoma (GBM), grade IV, is the highest grade and most common form. The diagnosis of diffuse gliomas has historically been based primarily on histopathologic features, yet these tumors have a wide range of biological behaviors that are only partially explained by morphology. Biomarkers have now become an established component of the neuropathologic diagnosis of gliomas, since molecular alterations aid in classification, prognostication and prediction of therapeutic response. Isocitrate dehydrogenase (IDH) mutations are frequent in grades II and III infiltrating gliomas of adults, as well as secondary GBMs, and are a major discriminate of biologic class. IDH mutant infiltrating astrocytomas (grades II and III), as well as secondary GBMs, are characterized by TP53 and ATRX mutations. Oligodendrogliomas are also IDH mutant, but instead are characterized by 1p/19q co-deletion and mutations of CIC, FUBP1, Notch1 and the TERT promoter. Primary GBMs typically lack IDH mutations and demonstrate EGFR, PTEN, TP53, PDGFRA, NF1 and CDKN2A/B alterations and TERT promoter mutations. Pediatric gliomas differ in their spectrum of disease from those in adults; high grade gliomas occurring in children frequently have mutations in H3F3A, ATRX and DAXX, but not IDH. Circumscribed, low grade gliomas, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma and ganglioglioma, need to be distinguished from diffuse gliomas in the pediatric population. These gliomas often harbor mutations or activating gene rearrangements in BRAF.
authors.affiliation: Department of Pathology and Laboratory Medicine, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Appin
authors.affiliation: Department of Pathology and Laboratory Medicine, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: dbrat@emory.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015321:Gene Rearrangement; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C498610:CIC protein, human; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; C497761:NOTCH1 protein, human; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D004265:DNA Helicases
keywords: 1p/19q; ATRX; Astrocytoma; BRAF; Biomarker; EGFR; Glioblastoma; Glioma; H3F3A; IDH; Oligodendroglioma; TERT; TP53