title: Cytogenetic and molecular genetic analyses of giant cell glioblastoma multiforme reveal distinct profiles in giant cell and non-giant cell subpopulations.
abstract: We have comparatively analyzed mechanisms associated with chromosomal and microsatellite instability in giant cell glioblastoma multiforme (gcGBM) and classic GBM. This included microsatellite instability (MSI), loss of expression of four major mismatch repair (MMR) proteins, aberrations of five chromosomes, EGFR copy number, and TP53 mutations. MSI was more frequent among gcGBM (30 vs. 7.8%, P = 0.054). TP53 mutations were more commonly observed in gcGBM (83.3%), whereas EGFR was amplified in just one gcGBM (8.3%). By tumor cell phenotype-specific cytogenetic analysis of gcGBM, increased chromosome copy numbers were identified in 72-84% of giant cells but in only 4-14% of nongiant cells; in classic GBM, intermediate frequencies were noted (11-49%). Chromosome 10 deletions were found in nongiant cells of all gcGBM cases but in only approximately 45% of the cell population in classic GBM. The present study shows a distinct pattern of cytogenetic alterations in nongiant and giant cell phenotypes in gcGBM and suggests that multinuclear giant cells evolve from nongiant tumor cells at an early tumor stage. Furthermore, the data point to differences in the profile of chromosomal and microsatellite instability in gcGBM and classic GBM that might underscore the distinct pathological features of both tumor subtypes.
authors.affiliation: Department of Neurosurgery, University of Dresden, Fetscherstr. 74, D-01307-Dresden, Germany. voelter.martinez@arcor.de
authors.forename: Ramon
authors.initials: R
authors.lastname: Martinez
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Roggendorf
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klein
authors.forename: Grisha
authors.initials: G
authors.lastname: Toedt
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D000368:Aged; D001483:Base Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D015726:Giant Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis; D011003:Ploidies; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D066246:ErbB Receptors; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein