PMID- 20540739 OWN - NLM STAT- MEDLINE DCOM- 20100816 LR - 20211020 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 10 DP - 2010 Jun 11 TI - Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors. PG - 280 LID - 10.1186/1471-2407-10-280 [doi] AB - 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 alpha, beta and gamma 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). FAU - Del Rey, Javier AU - Del Rey J AD - Departament de Biologia Cellular Fisiologia i Immunologia, Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain. FAU - Prat, Esther AU - Prat E FAU - Ponsa, Immaculada AU - Ponsa I FAU - Lloreta, Josep AU - Lloreta J FAU - Gelabert, Antoni AU - Gelabert A FAU - Algaba, Ferran AU - Algaba F FAU - Camps, Jordi AU - Camps J FAU - Miro, Rosa AU - Miro R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100611 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biomarkers, Tumor) RN - 0 (CCND1 protein, human) RN - 0 (Tubulin) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/*genetics MH - Centrosome/chemistry/*pathology MH - *Chromosomal Instability MH - *Chromosomes, Human, Pair 11 MH - Comparative Genomic Hybridization MH - Cyclin D1/*genetics MH - Female MH - Fluorescent Antibody Technique MH - *Gene Amplification MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Male MH - Micronuclei, Chromosome-Defective MH - Middle Aged MH - Mitosis MH - Neoplasm Staging MH - Paraffin Embedding MH - Prognosis MH - Time Factors MH - Tubulin/analysis MH - Urinary Bladder Neoplasms/chemistry/*genetics/mortality/*pathology PMC - PMC2906479 EDAT- 2010/06/15 06:00 MHDA- 2010/08/17 06:00 PMCR- 2010/06/11 CRDT- 2010/06/15 06:00 PHST- 2009/11/24 00:00 [received] PHST- 2010/06/11 00:00 [accepted] PHST- 2010/06/15 06:00 [entrez] PHST- 2010/06/15 06:00 [pubmed] PHST- 2010/08/17 06:00 [medline] PHST- 2010/06/11 00:00 [pmc-release] AID - 1471-2407-10-280 [pii] AID - 10.1186/1471-2407-10-280 [doi] PST - epublish SO - BMC Cancer. 2010 Jun 11;10:280. doi: 10.1186/1471-2407-10-280.