title: Giant cell glioblastoma is associated with altered aurora b expression and concomitant p53 mutation.
abstract: Giant cell glioblastoma (gcGB), a subtype of GB, is characterized by the presence of numerous multinucleated giant cells. The prognosis for gcGB is poor, but it may have a better clinical outcome compared with classic GB. The molecular alterations that lead to the multinucleated cell phenotype of gcGB have not been elucidated. Giant cell GB has a higher frequency of the tumor suppressor protein p53 mutations than GB, however, and a role for the mitotic Aurora B kinase has been suggested. We analyzed Aurora B expression in gcGB (n = 28) and GB (n = 54) patient tumor samples by immunohistochemistry; 17 gcGB and 22 GB samples were analyzed at the DNA and mRNA levels. No mutations in the Aurora B gene (AURKB) were found, but its mRNA and protein levels were significantly higher in gcGB than in GB. Fifty-nine percent of gcGB samples but only 18% of the GB samples showed p53 mutations. Ectopic overexpression of Aurora B induced a significant increase inthe proportion of multinucleated cells in p53 mutant U373-MG, but not in p53 wild-type U87-MG, glioma cells. RNAi of p53 in U87-MG cells led to an increase in the fraction of multinucleated cells that was further augmented by ectopic overexpression of Aurora B. These results suggest that loss of p53 function and dysregulated Aurora B protein levels might represent factors that drive the development of multinucleated cells in gcGB.
authors.affiliation: Department of Neurosurgery, Section Experimental Neurosurgery/Tumor Immunology, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Achim.Temme@uniklinikum-dresden.de
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.forename: Kathrin D
authors.initials: KD
authors.lastname: Geiger
authors.forename: Ralf
authors.initials: R
authors.lastname: Wiedemuth
authors.forename: Katharina
authors.initials: K
authors.lastname: Conseur
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tatsuka
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Hilmar
authors.initials: H
authors.lastname: Berger
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
mesh_terms: D000328:Adult; D000368:Aged; D064107:Aurora Kinase B; D064127:Aurora Kinases; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015726:Giant Cells / Q000378:metabolism*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases