title: Results of hyperamplification of centrosomes in naturally developing tumors of dogs.
abstract: OBJECTIVE
  To evaluate results of centrosome hyperamplification in naturally developing tumors of dogs.
  
  
  METHODS
  Tumor specimens from 9 dogs with tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary gland tumor) and 2 canine osteosarcoma cell lines.
  
  
  METHODS
  3 antibodies for centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin) were used for immunohistochemical analysis. Double immunostaining for centrosomes was used to confirm the specificity of these antibodies for centrosomes. Mutational analysis of the canine p53 gene was carried out by polymerase chain reaction-single-strand conformation polymorphism analysis, and expression of canine MDM2 protein was evaluated by use of immunohistochemical analysis, using anti-MDM2 antibody.
  
  
  RESULTS
  Immunohistochemical analysis of dog osteosarcoma cell lines with apparent aneuploidy revealed frequent hyperamplification of centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes were detected in the tumor tissues from all of the 9 tumors. The frequency of cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected.
  
  
  CONCLUSIONS
  Various types of naturally developing tumors in dogs often have hyperamplification of centrosomes associated with chromosome instability. Hyperamplification of centrosomes is a novel tumor marker for use in cytologic and histologic examinations of clinical specimens obtained from dogs.
authors.affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Setoguchi
authors.forename: M
authors.initials: M
authors.lastname: Okuda
authors.forename: E
authors.initials: E
authors.lastname: Nishida
authors.forename: M
authors.initials: M
authors.lastname: Yazawa
authors.forename: T
authors.initials: T
authors.lastname: Ishizaka
authors.forename: S H
authors.initials: SH
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Hisasue
authors.forename: R
authors.initials: R
authors.lastname: Nishimura
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: K
authors.initials: K
authors.lastname: Masuda
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D018385:Centrosome / Q000473:pathology*; D002869:Chromosome Aberrations / Q000662:veterinary*; D004273:DNA, Neoplasm / Q000737:chemistry; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D007150:Immunohistochemistry / Q000662:veterinary; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics / Q000662:veterinary*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D051736:Proto-Oncogene Proteins c-mdm2