title: Copy number analysis of 24 oncogenes: MDM4 identified as a putative marker for low recurrence risk in non muscle invasive bladder cancer.
abstract: Patients with non-muscle invasive bladder cancer (NMIBC) generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs) of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF) using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB) were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher's test p=0.023). Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p=0.041). Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. samanta.salvi@irst.emr.it.
authors.forename: Samanta
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. daniele.calistri@irst.emr.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. giorgia.gurioli@irst.emr.it.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gurioli
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. elisa.carretta@irst.emr.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Carretta
authors.affiliation: Pathology Unit, Morgagni Pierantoni Hospital, Forlì 47121, Italy. l.serra@ausl.fo.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Serra
authors.affiliation: Department of Urology, Morgagni Pierantoni Hospital, Forli 47121, Italy. fiorifo@tin.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gunelli
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. wainer.zoli@irst.emr.it.
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy. valentina.casadio@irst.emr.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Casadio
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins