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Open Access Research article

Chromosomal imbalances in human bladder urothelial carcinoma: similarities and differences between biopsy samples and cancer stem-like cells

Donatella Conconi1, Elena Panzeri1, Serena Redaelli1, Giorgio Bovo2, Paolo Viganò3, Guido Strada3, Leda Dalprà1 and Angela Bentivegna1*

Author Affiliations

1 Department of Surgery and Translational Medicine, University of Milan-Bicocca, via Cadore 48, 20052 Monza, Italy

2 Depatment of Pathology, S. Gerardo Hospital, Monza, Italy

3 Urology Division, Bassini Icp Hospital, Milano, Italy

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BMC Cancer 2014, 14:646  doi:10.1186/1471-2407-14-646

Published: 1 September 2014

Abstract

Background

The existence of two distinct groups of tumors with different clinical characteristic is a remarkable feature of transitional cell carcinomas (TCCs) of the bladder. More than 70% are low-grade (LG) non-infiltrating (NI) cancers at diagnosis, but 60-80% of them recur at least one time and 10-20% progress in stage and grade. On the other hand, about 20% of tumors show muscle invasion (IN) and have a poor prognosis with <50% survival after 5 years. This study focuses on the complexity of the bladder cancer genome, and for the first time to our knowledge, on the possibility to compare genomic alterations of in vitro selected cancer stem-like cells (CSCs), and their original biopsy in order to identify different genomic signature already present in the early stages of tumorigenesis of LG and HG tumors.

Methods

We initially used conventional chromosome analysis on TCC biopsies with different histotypes (LG vs HG) in order to detect rough differences between them. Then, we performed array comparative genomic hybridization (aCGH) on 10 HG and 10 LG tumors providing an overview of copy number alterations (CNAs). Finally, we made a comparison of the overall CNAs in 16 biopsies and their respective CSCs isolated from them.

Results

Our findings indicate that LG and HG bladder cancer differ with regard to their genomic profile even in the early stage of tumorigenesis; moreover, we identified a subgroup of LG samples with a higher tendency to lose genomic regions which could represent a more aggressive phenotype.

Conclusions

The outcomes not only provide valuable information to deeper studying TCC carcinogenesis, but also could help in the clinic for diagnosis and prognosis of patients who will benefit from a more aggressive therapy.

Keywords:
Transitional Cell Carcinoma; Array Comparative Genomic Hybridization; DNA copy number alterations; cancer stem like-cells