CASE REPORT Open Access DNA copy number alterations and PPARG amplification in a patient with multifocal bladder urothelial carcinoma Donatella Conconi 1,2† , Elena Panzeri 1,2† , Serena Redaelli 1,2 , Giorgio Bovo 3 , Marco Volante 4 , Paolo Viganò 5 , Guido Strada 5 , Leda Dalprà 1,2 and Angela Bentivegna 1,2* Abstract Background: Bladder cancer is the seventh most common cancer worldwide and over 90% are transitional cell carcinoma (TCC). At the first time of diagnosis at least 70% of TCC present as superficial bladder cancer. Because the clinical outcome of superficial bladder tumors is relatively unpredictable, there is a pressing need to identify markers that may predict tumor recurrence and progression and new treatment strategies. Case presentation: We present a unique case of a 67-year old male who underwent total cystectomy after repeated trans-urethral resections of the bladder for multifocal non-muscle invasive bladder cancer. The first and the third tumor were diagnosed as high grade non-infiltrating (HGNI), while the second as carcinoma in situ (CIS). We performed both array comparative genomic hybridization and a targeted chromosomal profile by UroVysion in order to detect copy number variations (CNVs) that may be involved with tumor recurrence and progression. The overall data from this study provide new evidence for the monoclonal origin of urothelial tumor multifocality as several genetic changes were found in different tumors of the same patient. From the analysis of shared CNVs two gained regions emerged at 3p25.2 and 12q23.2, including PPARG and ASCL1 genes, respectively. The copy number level of these genes would seem inversely mutually correlated and highly dependent on histological grade, because the highest level of amplification at 3p25.2 was evidenced in the two HGNI samples, while the highest level of copy number gain at 12q23.2 was reported in the CIS. Conclusion: We provide new evidence on the role of PPARG in initiation and maintenance of bladder cancer. For the first time we also suggest a possible explanation for the elevated expression of PPARG in this type of tumor through a focal high level amplification at 3p25.2. Furthermore, a new gene, ASCL1, emerged as a potential candidate to assist PPARG in bladder carcinogenesis. Keywords: Multifocal non-muscle-invasive bladder cancer, Transitional cell carcinoma, Array-CGH, DNA copy number variations, PPARG, FISH Background Bladder cancer is the seventh most common cancer worldwide and the fourth most common cancer diag- nosed in men in the USA and European countries [1]. Over 90% of bladder cancers are transitional cell carcin- oma (TCC), and at the first time of diagnosis, at least 70% of TCC present as superficial tumors confined to the mucosa (pTa disease) or lamina propria (pT1). In the remaining cases, tumors present as muscle invasive dis- ease (≥pT2) with no history of superficial disease. Low- grade pTa tumors have a high risk of recurrence (70%) but rarely progress to muscle-invasive tumors, con- versely high-grade pTa and pT1 tumors show a high risk of progression [2]. Because the clinical outcome is relatively unpredict- able and the limitations of current therapeutic options, there is a pressing need to identify markers that may * Correspondence: angela.bentivegna@unimib.it † Equal contributors 1 Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, Monza, Italy 2 Medical Genetics Laboratory, S. Gerardo Hospital, Monza, Italy Full list of author information is available at the end of the article © 2012 Conconi et al.; licensee 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. Conconi et al. BMC Research Notes 2012, 5:607 http://www.biomedcentral.com/1756-0500/5/607