title: Aberrations of BUBR1 and TP53 gene mutually associated with chromosomal instability in human colorectal cancer.
abstract: OBJECTIVE
  Defects in mitotic checkpoint and p53-dependent pathways associate with chromosomal instability. In the present study, we investigated the interplay between BUBR1 and p53 and their association with genetic instability in colorectal cancer.
  
  
  METHODS
  139 colorectal cases were examined for BUBR1, p53 and genetic instability indicators. BUBR1 expression was evaluated by immunohistochemistry and TP53 gene was directly sequenced. DNA ploidy was studied by laser scanning cytometry; MSI and TP53 loss of heterozygosity was also examined.
  
  
  RESULTS
  64% of cases had high BUBR1 expression and were associated with the TP53 mutation. High BUBR1 expression and TP53 mutation associated with DNA aneuploidy and showed an inverse association with MSI. Cases with high BUBR1 expression and TP53 mutation had profound aneuploidy phenotypes and less frequent MSI compared to cases with one or neither aberration.
  
  
  CONCLUSIONS
  Our findings indicated an interplay between BUBR1 and p53 in colorectal cancer. Altered expression of both molecules was associated with chromosomal instability.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan The Third Surgery Department, Liaoning Cancer Hospital and Institute, Shenyang, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan okieiji@surg2.med.kyushu-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Chugai Research Institute for Medical Science, Inc., Gotnemba, Japan.
authors.forename: Ayae
authors.initials: A
authors.lastname: Ikawa-Yoshida
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ida
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000368:Aged; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: BUBR1; Chromosomal instability; TP53 gene; colorectal cancer; microsatellite instability