Genomic Characterization of Upper Tract Urothelial Carcinoma

Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.

To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.

Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes

We described co-mutation patterns and copy number alterations in UTUC We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102)

Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations Genes altered more commonly in high-grade UTUC included FGFR3 (35 6% vs 21 6%; p=0 065), HRAS (13 6% vs 1 0%; p=0 001), and CDKN2B (15 3% vs 3 9%; p=0 016) Genes less frequently mutated in high-grade UTUC included TP53 (25 4% vs 57 8%; p

High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1 As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma

Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies

European urology 2015 Aug 13 [Epub ahead of print]

John P Sfakianos, Eugene K Cha, Gopa Iyer, Sasinya N Scott, Emily C Zabor, Ronak H Shah, Qinghu Ren, Aditya Bagrodia, Philip H Kim, A Ari Hakimi, Irina Ostrovnaya, Ricardo Ramirez, Aphrothiti J Hanrahan, Neil B Desai, Arony Sun, Patrizia Pinciroli, Jonathan E Rosenberg, Guido Dalbagni, Nikolaus Schultz, Dean F Bajorin, Victor E Reuter, Michael F Berger, Bernard H Bochner, Hikmat A Al-Ahmadie, David B Solit, Jonathan A Coleman

Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA Electronic address: chae@mskcc org , Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy , Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Department of Epidemiology and Biostatistics, Computational Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Weill Medical College of Cornell University, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA

PubMed

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