title: Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma.
abstract: Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH) results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs) present in biopsies and retained in the corresponding cancer stem cell (CSC) subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. donatella.conconi@unimib.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Conconi
authors.affiliation: Medical Genetics Laboratory, San Gerardo Hospital, 20900 Monza, Italy. elena.sala@hsgerardo.org.
authors.forename: Elena
authors.initials: E
authors.lastname: Sala
authors.affiliation: Department of Pathology, San Gerardo Hospital, 20900 Monza, Italy. g.bovo@hsgerardo.org.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.affiliation: Urology Division, Bassini Icp Hospital, 20092 Cinisello Balsamo, Italy. guido.strada@icp.mi.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Strada
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. leda.dalpra@unimib.it.|Medical Genetics Laboratory, San Gerardo Hospital, 20900 Monza, Italy. leda.dalpra@unimib.it.
authors.forename: Leda
authors.initials: L
authors.lastname: Dalprà
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. marialuisa.lavitrano@unimib.it.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Lavitrano
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. angela.bentivegna@unimib.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Bentivegna
mesh_terms: D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D019927:Cyclin E / Q000235:genetics; D056915:DNA Copy Number Variations; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D015513:Oncogene Proteins / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D019927:Cyclin E; D015513:Oncogene Proteins; D047495:PPAR gamma; D051736:Proto-Oncogene Proteins c-mdm2; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; C475820:CCNE1 protein, human; C497206:MDM2 protein, human; C508053:ERBB2 protein, human
keywords: bladder cancer; cancer stem cells; copy number alterations; therapeutic targets; transitional cell carcinomas