Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

International Journal of Molecular Sciences

Samanta Salvi²  Daniele Calistri²  Giorgia Gurioli²  Elisa Carretta³  Luigi Serra¹  Roberta Gunelli⁴  Wainer Zoli² 

[1] Pathology Unit, Morgagni Pierantoni Hospital, Forlì 47121, Italy; E-Mail:;Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; E-Mails:;Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; E-Mail:;Department of Urology, Morgagni Pierantoni Hospital, Forli 47121, Italy; E-Mail:

关键词: NMIBC;    recurrence;    multiplex ligation probe amplification (MLPA);    MDM4;   

DOI  :  10.3390/ijms150712458

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.