Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
  • 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
  • Núria Malats
  • Francisco X. Real
  • Ellen C. Zwarthoff
  • Torben Falck Ørntoft
  • Lars Dyrskjøt
Organisations
External organisations
  • Aarhus University Hospital
  • Autonomous University of Barcelona
  • Frederiksberg Hospital
  • Spanish National Cancer Research Center (CNIO)
  • Uppsala University
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Klinikum rechts der Isar
  • University of Belgrade
  • Saarland University
  • Friedrich Schiller University Jena
  • Aalborg University Hospital
  • University of Vic
  • Erasmus University Medical Center
  • Pompeu Fabra University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics
Original languageEnglish
Pages (from-to)27-42
Number of pages16
JournalCancer Cell
Volume30
Issue number1
Publication statusPublished - 2016 Jul 11
Publication categoryResearch
Peer-reviewedYes