Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors

BMC Cancer

Research Article

Antoni Gelabert¹  Javier del Rey²  Esther Prat²  Immaculada Ponsa²  Rosa Miró²  Jordi Camps³  Ferran Algaba⁴  Josep Lloreta⁵ 

[1] Departament d'Urologia, Hospital del Mar, IMAS UAB, Passeig Marítim 25-29 08003, Barcelona, Spain;Departament de Biologia Cellular Fisiologia i Immunologia, Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;Departament de Biologia Cellular Fisiologia i Immunologia, Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;Genetics Branch, Center for Cancer Research, National Cancer Institute/NIH, 50 South Drive, 20892, Bethesda, MD, USA;Departament de Patologia, Fundació Puigvert, Universitat Autònoma de Barcelona, Cartagena 340-350, 08025, Barcelona, Spain;Departament de Patologia, Hospital del Mar, IMAS, Universitat Pompeu Fabra, Passeig Marítim 25-29, 08003, Barcelona, Spain;

关键词: Comparative Genomic Hybridization;    Bladder Tumor;    Centrosome Amplification;    CCND1 Gene;    CCND1 Amplification;   

DOI  :  10.1186/1471-2407-10-280

 received in 2009-11-24, accepted in 2010-06-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAneuploidy, 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.MethodsTwenty-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.ResultsBased 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.ConclusionsComplex 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).

【 授权许可】

Unknown   
© del Rey et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.