Molecular-genetic classification of gliomas and its practical application to diagnostic neuropathology

José E. Velázquez Vega, Daniel Jay Brat

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Gliomas represent a broad category of tumors affecting the central nervous system of patients of all ages. Those that are diffusely infiltrative, such as the diffuse astrocytomas and oligodendrogliomas, occur most frequently in the cerebral hemispheres of adults and have a strong tendency toward clinical progression. The highest grade form, glioblastoma (GBM), WHO grade IV, has a dismal prognosis and can present either de novo or evolve from a lower grade precursor. The classification and grading of diffuse gliomas has historically been based primarily on histopathologic features, yet molecular biomarkers have now become an established component of the neuropathologic diagnosis, since molecular alterations are more reproducible classifiers and provide additional value in prognostication and prediction of therapeutic response. Isocitrate dehydrogenase (IDH) mutations are frequent in grade II and III diffuse gliomas of adults, as well as secondary GBMs, and are a major discriminate of biologic class. IDH-mutant diffusely infiltrative 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 codeletion 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. Low grade neuroepithelial tumors of childhood, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, ganglioglioma, dysembryoplastic neuroepithelial tumor and angiocentric glioma have molecular pathogenesis and clinical behavior distinct from adult gliomas often harbor mutations or activating gene rearrangements in BRAF, FGFR1 and MYB.

Original languageEnglish (US)
Title of host publicationDiffuse Low-Grade Gliomas in Adults
PublisherSpringer International Publishing
Pages73-100
Number of pages28
ISBN (Electronic)9783319554662
ISBN (Print)9783319554648
DOIs
StatePublished - Jul 3 2017

Keywords

  • 1p/19q codeletion
  • Biomarker
  • Glioblastoma
  • IDH mutation
  • Infiltrating glioma
  • Moleculargenetic
  • Neuroepithelial tumor

ASJC Scopus subject areas

  • Medicine(all)

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