title: GAS41 amplification results in overexpression of a new spindle pole protein.
abstract: Amplification is a hallmark of many human tumors but the role of most amplified genes in human tumor development is not yet understood. Previously, we identified a frequently amplified gene in glioma termed glioma-amplified sequence 41 (GAS41). Using the TCGA data portal and performing experiments on HeLa and TX3868, we analyzed the role of GAS41 amplification on GAS41 overexpression and the effect on the cell cycle. Here we show that GAS41 amplification is associated with overexpression in the majority of cases. Both induced and endogenous overexpression of GAS41 leads to an increase in multipolar spindles. We showed that GAS41 is specifically associated with pericentrosome material. As result of an increased GAS41 expression we found bipolar spindles with misaligned chromosomes. This number was even increased by a combined overexpression of GAS41 and a reduced expression of NuMA. We propose that GAS41 amplification may have an effect on the highly altered karyotype of glioblastoma via its role during spindle pole formation.
authors.affiliation: Department of Human Genetics, Saarland University, Medical School, Homburg, Germany. jana.schmitt@uks.eu
authors.forename: Jana
authors.initials: J
authors.lastname: Schmitt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fischer
authors.forename: Sabrina
authors.initials: S
authors.lastname: Heisel
authors.forename: Hilmar
authors.initials: H
authors.lastname: Strickfaden
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.forename: Alessia
authors.initials: A
authors.lastname: Ruggieri
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Paul
authors.initials: P
authors.lastname: Chang
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics*; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D008941:Spindle Apparatus; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D014157:Transcription Factors; C109446:YEATS4 protein, human