期刊
MOLECULAR ASPECTS OF MEDICINE
卷 45, 期 -, 页码 87-96出版社
ELSEVIER
DOI: 10.1016/j.mam.2015.05.002
关键词
Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma; Biomarker; IDH; ATRX; TP53; TERT; EGFR; H3F3A; BRAF; 1p/19q
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 re-arrangements in BRAF. (C) 2015 Elsevier Ltd. All rights reserved.
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