Comparative Genomic Hybridization Analysis Reveals New Different Subgroups in Early-stage Bladder Tumors - 20/08/11

Doi : 10.1016/j.urology.2009.04.080

Esther Prat ^a, Javier del Rey ^a, Immaculada Ponsa ^a, Marga Nadal ^b, Jordi Camps ^a, Alberto Plaja ^c, Mercedes Campillo ^d, Ferran Algaba ^e, Antoni Gelabert ^f, Rosa Miró ^a,^⁎
^a Institut de Biotecnologia i Biomedicina and Department de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain
^b Laboratori de Recerca translacional, Institut Català d'Oncologia-IDIBELL, Hospital Duran i Reynals, Barcelona, Spain
^c Programa de Medicina Molecular i Genètica, Hospital Vall d'Hebron, Barcelona, Spain
^d Laboratori de Medicina Computacional, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
^e Servei d'Anatomia Patològica, Fundació Puigvert, Barcelona, Spain
^f Department d'Urologia, Hospital del Mar, IMAS-UAB, Barcelona, Spain

Reprint requests: Rosa Miró, Ph.D., Institut de Biotecnologia i Biomedicina and Department de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain 08193

Résumé

Objectives

To classify bladder tumors according to their genomic imbalances and evaluate their association with patient's outcome.

Methods

Sixty-three superficially and minimally invasive bladder tumors were analyzed by conventional comparative genomic hybridization. Subtelomeric screening in 15 of these tumors was performed by multiplex ligation-dependent probe amplification.

Results

Losses of 9q and 9p (32% and 25% of all cases, respectively) as well as gains of chromosomes Xq and Xp (28% and 25%, respectively) were the most frequent chromosome imbalances. Losses of 8p and gains in 1q and 8q were detected in >20% of cases. Tumors were classified into 3 groups according to their individualized pattern of gains and losses. The largest group was characterized by few chromosome imbalances, presenting 77% and 49% of the Ta and T1 tumors, respectively. Another group characterized by chromosomal gains, was composed of equal number of Ta and T1 tumors, with +1q and +17q gains being the most common imbalances. A minority group was characterized by chromosomal losses on 11q, 5q, and 6q. The multiplex ligation-dependent probe amplification study showed good correlation with comparative genomic hybridization results. With regard to the biological significance of this classification, a remarkable fact is that this minority group composed mainly of T1 tumors, showed a significant decrease in patient overall survival.

Conclusions

Our data suggest that superficial carcinomas of the bladder can be subdivided into a larger number of subclasses than had previously been expected. Our results also demonstrate a decreased survival among patients whose tumors show more genomic losses than gains.

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Plan

Material and Methods

Patients and Methods

Comparative Genomic Hybridization

Multiplex Ligation-Dependent Probe Amplification

	This study has been partially supported by ISCIII: EPICUR-Red (G03/174), PI020263, and RD06/0020/1020 and “Agència de Gestió d'Ajuts Universitaris, de Recerca-AGAUR” (2005SGR00495); by the Institut Municipal d'Investigacions Mèdiques (to E.P.) and the Generalitat de Catalunya (to J.R.).
	J.C. was a fellow of the EPICUR-Red research program.
	E. Prat. and J. del Rey contributed equally to this study.