Centrosome clustering and Cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors
Del Rey Azpiri, Javier (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Prat Pedrola, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ponsa Arjona, Immaculada (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Lloreta, Josep, 1958- (Universitat Pompeu Fabra. Departament de Patologia)
Gelabert Mas, Antonio (Hospital del Mar (Barcelona, Catalunya))
Algaba, Ferran (Universitat Autònoma de Barcelona. Departament de Patologia i de Producció Animals)
Camps Polo, Jordi (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Miró, Rosa (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Fecha:	2010
Resumen:	Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0. 001).
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Lengua:	Anglès
Documento:	Article ; Versió publicada
Publicado en:	BMC Cancer, Vol. 10, N. 280 (June 2010) , p. 1-11, ISSN 1471-2407

DOI: 10.1186/1471-2407-10-280
PMID: 20540739

11 p, 1016.0 KB

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