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Detection of centrosome amplification as a surrogate marker of dysfunction in the p53 pathway –p53 gene mutation or MDM2 overexpression
Authors:N Kaneko  M Okuda  N Toyama  T Oikawa  M Watanabe  N Kanaya  M Yazawa  K Hasegawa  M Morimoto  T Hayashi  S Une  M Nakaichi  Y Taura  H Tsujimoto  H Inokuma
Institution:Laboratories of Veterinary Internal Medicine, Faculty of Agriculture, Yamaguchi University, Yoshida, Yamaguchi, Japan; Department of Veterinary Surgery, Graduate Schools of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan; Department of Veterinary Internal Medicine, Graduate Schools of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan; Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, Yoshida, Yamaguchi, Japan; Veterinary Surgery, Faculty of Agriculture, Yamaguchi University, Yoshida, Yamaguchi, Japan
Abstract:In human and canine cancers, the inactivation of p53 protein as well as p53 gene mutation and MDM2 overexpression result in centrosome amplification that in turn contributes to chromosomal instability. To explore the usefulness of the detection of centrosome amplification as a surrogate marker of dysfunction in the p53 pathway, we systematically analysed centrosome amplification, p53 overexpression, p53 gene mutation and MDM2 overexpression in canine tumours. Centrosome amplification was detected in 16 of 51 (31%) naturally developing tumours in dogs. All the tumour specimens with aberrations in the p53 pathway, including p53 overexpression, p53 gene mutation or MDM2 overexpression, showed centrosome amplification, suggesting that the detection of centrosome amplification could serve as a preliminary surrogate marker of dysfunction in the p53 pathway.
Keywords:cancer  centrosome  MDM2              p53 gene  p53 protein
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