title: Gliosarcomas lack BRAFV600Emutation, but a subset exhibit β-catenin nuclear localization.
abstract: Gliosarcoma (GS) is a rare subtype of glioblastoma (GBM) characterized by both glial and mesenchymal components. Unlike GBM, there are no specific prognostic markers, and optimized treatments for patients with GS do not exist. Recent reports describe BRAFV600Emutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (β-catenin gene) mutations have been described in GBM. We sought to determine whether GS tumors harbor BRAFV600Emutations or aberrant Wnt signaling, as indicated by nuclear localization of β-catenin, by immunohistochemical detection. Forty-eight (48) cases of primary and secondary adult GS (including recurrent ones) were evaluated by immunohistochemical techniques for the presence of nuclear β-catenin and the BRAFV600Emutation. A small subset (6/46, 13%) showed nuclear localization of β-catenin. None of the cases harbored BRAFV600Emutations (0/48). These results are the first to describe the presence of Wnt signaling pathway abnormalities, manifested by nuclear β-catenin, in a subset, as well as the lack of BRAFV600Emutation in GS. We propose a potential role for Wnt pathway alterations in the pathogenesis of a subset of GS.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Schwetye
authors.affiliation: Department of Pathology, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Joseph
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Hussam
authors.initials: H
authors.lastname: Al-Kateb
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Department of Pathology, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D018316:Gliosarcoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF-V600E; WNT pathway; beta-catenin; glioblastoma; gliosarcoma