title: Overexpressed Skp2 within 5p amplification detected by array-based comparative genomic hybridization is associated with poor prognosis of glioblastomas.
abstract: To better understand the pathogenesis of glioblastoma multiforme (GBM) and to increase the accuracy of predicting outcomes for patients with this disease, we performed genome-wide screening for DNA copy-number aberrations in 22 glioma-derived cell lines using a custom-made comparative genomic hybridization-array. Copy-number gains were frequently detected at 3q, 7p, 7q, 20q, Xp and Xq, and losses at 4q, 9p, 10p, 10q, 11q, 13q, 14q, 18q, and 22q. Among several non-random chromosomal aberrations, the gain/amplification of DNA at 5p, which has never been reported before in GBM, was detected with a relatively high ratio (log2 ratio = 0.41-1.19) in four cell lines. Amplification and subsequent overexpression of SKP2, a possible target of amplification within 5p, were detected in four of the 22 cell lines. We also investigated the expression of the gene product in primary GBM by immunohistochemistry, which revealed increased levels of Skp2 in 11 of the 35 tumors examined (31.4%). Heightened expression of Skp2 was associated with shorter overall survival (P = 0.001, logrank test), especially in patients younger than 65 years. These results suggest that overexpression of Skp2 through gene amplification may contribute to the pathogenesis of GBM, and that overabundance of the protein might be a useful prognostic tool in patients with this disease.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Saigusa
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Sana
authors.initials: S
authors.lastname: Yokoi
authors.forename: Motohiko
authors.initials: M
authors.lastname: Maruno
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.forename: Masaru
authors.initials: M
authors.lastname: Aoyagi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Ohno
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002895:Chromosomes, Human, Pair 5; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D044786:S-Phase Kinase-Associated Proteins