Molecular Pathways in Gliomagenesis and Their Relevance to Neuropathologic Diagnosis. (January 2015)

• Record Type: Journal Article
• Authors: Appin, Christina L.; Brat, Daniel J.
• Is Part Of: Advances in anatomic pathology. Volume 22:Number 1(2015)
• Publication Date: 2015-01
• Subjects: Pathology -- Periodicals; 616.0705
• DOI: 10.1097/PAP.0000000000000048
• Languages: English
• ISSNs: 1072-4109

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Gliomas are a large and diverse group of primary brain tumors that include those that are diffusely infiltrative and others that are well-circumscribed and low grade. Diffuse gliomas are currently classified by the World Health Organization as astrocytomas, oligodendrogliomas, or oligoastrocytomas and range in grade from II to IV. Glioblastoma (GBM), World Health Organization grade IV, is the highest grade and most common form of astrocytoma. In the past, the diagnosis of gliomas was almost exclusively based on histopathologic features. More recently, improved understanding of molecular genetic underpinnings has led to ancillary molecular studies becoming standard for classification, prognostication, and predicting therapy response. Isocitrate dehydrogenase (<italic>IDH</italic>) mutations are frequent in grade II and III infiltrating gliomas and secondary GBMs. Infiltrating astrocytomas and secondary GBMs are characterized by <italic>IDH</italic>, <italic>TP53</italic>, and <italic>ATRX</italic> mutations, whereas oligodendrogliomas demonstrate 1p/19q codeletion and mutations in <italic>IDH</italic>, <italic>CIC</italic>, <italic>FUBP1</italic>, and the <italic>telomerase reverse transcriptase</italic> (<italic>TERT</italic>) promoter. Primary GBMs typically lack <italic>IDH</italic> mutations and are instead characterized by <italic>EGFR</italic>, <italic>PTEN</italic>, <italic>TP53</italic>, <italic>PDGFRA</italic>, <italic>NF1</italic>, and <italic>CDKN2A/B</italic> alterations and <italic>TERT</italic> promoter mutations. Pediatric GBMs differ from those in adults and frequently have mutations in <italic>H3F3A</italic>, <italic>ATRX</italic>, and <italic>DAXX</italic>, but not <italic>IDH.</italic> In contrast, circumscribed, low-grade gliomas of childhood, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often harbor mutations or activating gene rearrangements in <italic>BRAF</italic>. Neuropathologic assessment of gliomas increasingly relies on ancillary testing of molecular alterations for proper classification and patient management.</p> </sec> </abstract>