title: Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy.
abstract: BACKGROUND
  Aneuploidy and chromosomal instability (CIN) are common abnormalities in human cancer. Alterations of the mitotic spindle checkpoint are likely to contribute to these phenotypes, but little is known about somatic alterations of mitotic spindle checkpoint genes in breast cancer.
  
  
  METHODS
  To obtain further insight into the molecular mechanisms underlying aneuploidy in breast cancer, we used real-time quantitative RT-PCR to quantify the mRNA expression of 76 selected mitotic spindle checkpoint genes in a large panel of breast tumor samples.
  
  
  RESULTS
  The expression of 49 (64.5%) of the 76 genes was significantly dysregulated in breast tumors compared to normal breast tissues: 40 genes were upregulated and 9 were downregulated. Most of these changes in gene expression during malignant transformation were observed in epithelial cells.Alterations of nine of these genes, and particularly NDC80, were also detected in benign breast tumors, indicating that they may be involved in pre-neoplastic processes.We also identified a two-gene expression signature (PLK1 + AURKA) which discriminated between DNA aneuploid and DNA diploid breast tumor samples. Interestingly, some DNA tetraploid tumor samples failed to cluster with DNA aneuploid breast tumors.
  
  
  CONCLUSIONS
  This study confirms the importance of previously characterized genes and identifies novel candidate genes that could be activated for aneuploidy to occur. Further functional analyses are required to clearly confirm the role of these new identified genes in the molecular mechanisms involved in breast cancer aneuploidy. The novel genes identified here, and/or the two-gene expression signature, might serve as diagnostic or prognostic markers and form the basis for novel therapeutic strategies.
authors.affiliation: INSERM U735, Institut Curie Hôpital René Huguenin, St-Cloud, France. ivan.bieche@curie.net
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: François
authors.initials: F
authors.lastname: Lallemand
authors.forename: Sengül
authors.initials: S
authors.lastname: Tozlu-Kara
authors.forename: Hind
authors.initials: H
authors.lastname: Bennani
authors.forename: Michèle
authors.initials: M
authors.lastname: Beuzelin
authors.forename: Keltouma
authors.initials: K
authors.lastname: Driouch
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.forename: Hugues
authors.initials: H
authors.lastname: Ripoche
authors.forename: Géraldine
authors.initials: G
authors.lastname: Cizeron-Clairac
authors.forename: Frédérique
authors.initials: F
authors.lastname: Spyratos
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
mesh_terms: D000782:Aneuploidy; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D008941:Spindle Apparatus / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger