title: Clinical implication of centrosome amplification and expression of centrosomal functional genes in multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers.
  
  
  METHODS
  A total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs.
  
  
  RESULTS
  Based on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019). Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes: AURKB, PLK4, TUBG1 (P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes: AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT, and TACC3 (P < 0.05).
  
  
  CONCLUSIONS
  Our findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.
authors.affiliation: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5/A3, Brno, 62500, Czech Republic.
authors.forename: Elena
authors.initials: E
authors.lastname: Dementyeva
authors.forename: Fedor
authors.initials: F
authors.lastname: Kryukov
authors.forename: Lenka
authors.initials: L
authors.lastname: Kubiczkova
authors.forename: Pavel
authors.initials: P
authors.lastname: Nemec
authors.forename: Sabina
authors.initials: S
authors.lastname: Sevcikova
authors.forename: Ivana
authors.initials: I
authors.lastname: Ihnatova
authors.forename: Jiri
authors.initials: J
authors.lastname: Jarkovsky
authors.forename: Jiri
authors.initials: J
authors.lastname: Minarik
authors.forename: Zdena
authors.initials: Z
authors.lastname: Stefanikova
authors.forename: Petr
authors.initials: P
authors.lastname: Kuglik
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002469:Cell Separation; D018385:Centrosome / Q000648:ultrastructure*; D004260:DNA Repair; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012008:Recurrence; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D053668:Syndecan-1