Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.

Cancer cell. 2016 Jun 16 [Epub ahead of print]

Jakob Hedegaard, Philippe Lamy, Iver Nordentoft, Ferran Algaba, Søren Høyer, Benedicte Parm Ulhøi, Søren Vang, Thomas Reinert, Gregers G Hermann, Karin Mogensen, Mathilde Borg Houlberg Thomsen, Morten Muhlig Nielsen, Mirari Marquez, Ulrika Segersten, Mattias Aine, Mattias Höglund, Karin Birkenkamp-Demtröder, Niels Fristrup, Michael Borre, Arndt Hartmann, Robert Stöhr, Sven Wach, Bastian Keck, Anna Katharina Seitz, Roman Nawroth, Tobias Maurer, Cane Tulic, Tatjana Simic, Kerstin Junker, Marcus Horstmann, Niels Harving, Astrid Christine Petersen, M Luz Calle, Ewout W Steyerberg, Willemien Beukers, Kim E M van Kessel, Jørgen Bjerggaard Jensen, Jakob Skou Pedersen, Per-Uno Malmström, Núria Malats, Francisco X Real, Ellen C Zwarthoff, Torben Falck Ørntoft, Lars Dyrskjøt

Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Section of Pathology, Fundació Puigvert, University Autonoma de Barcelona, Barcelona 08025, Spain., Department of Pathology, Aarhus University Hospital, Aarhus 8000, Denmark., Department of Pathology, Aarhus University Hospital, Aarhus 8000, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Urology, Frederiksberg Hospital, Frederiksberg 2000, Denmark., Department of Urology, Frederiksberg Hospital, Frederiksberg 2000, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain., Department of Surgical Sciences, Uppsala University, Uppsala 75185, Sweden., Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund 22100, Sweden., Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund 22100, Sweden., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Urology, Aarhus University Hospital, Aarhus 8200, Denmark., Institute of Pathology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Erlangen 91054, Germany., Institute of Pathology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Erlangen 91054, Germany., Department of Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Erlangen 91054, Germany., Department of Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Erlangen 91054, Germany., Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Munich 81675, Germany., Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Munich 81675, Germany., Department of Urology, Klinikum rechts der Isar der Technischen Universität München, Munich 81675, Germany., Faculty of Medicine, Clinic of Urology, Clinical Centre of Serbia, University of Belgrade, 11000 Belgrade, Serbia., Faculty of Medicine, Institute of Medical and Clinical Biochemistry, University of Belgrade, 11000 Belgrade, Serbia., Department of Urology, Saarland University, Homburg 66421, Germany., Department of Urology, Friedrich-Schiller-University Jena, Jena 07737, Germany., Department of Urology, Aalborg University Hospital, Aalborg 9000, Denmark., Department of Pathology, Aalborg University Hospital, Aalborg 9000, Denmark., Systems Biology Department, University of Vic, Vic, Barcelona 08500, Spain., Department of Public Health, Erasmus Medical Centre, 3015 CE Rotterdam, the Netherlands., Department of Pathology, Erasmus Medical Centre, 3015 CE Rotterdam, the Netherlands., Department of Pathology, Erasmus Medical Centre, 3015 CE Rotterdam, the Netherlands., Department of Urology, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Surgical Sciences, Uppsala University, Uppsala 75185, Sweden., Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain., Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain., Department of Pathology, Erasmus Medical Centre, 3015 CE Rotterdam, the Netherlands., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark. Electronic address: .

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