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. 2016 Jul 11;30(1):27-42.
doi: 10.1016/j.ccell.2016.05.004. Epub 2016 Jun 16.

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Jakob Hedegaard  1 , Philippe Lamy  1 , Iver Nordentoft  1 , Ferran Algaba  2 , Søren Høyer  3 , Benedicte Parm Ulhøi  3 , Søren Vang  1 , Thomas Reinert  1 , Gregers G Hermann  4 , Karin Mogensen  4 , Mathilde Borg Houlberg Thomsen  1 , Morten Muhlig Nielsen  1 , Mirari Marquez  5 , Ulrika Segersten  6 , Mattias Aine  7 , Mattias Höglund  7 , Karin Birkenkamp-Demtröder  1 , Niels Fristrup  1 , Michael Borre  8 , Arndt Hartmann  9 , Robert Stöhr  9 , Sven Wach  10 , Bastian Keck  10 , Anna Katharina Seitz  11 , Roman Nawroth  11 , Tobias Maurer  11 , Cane Tulic  12 , Tatjana Simic  13 , Kerstin Junker  14 , Marcus Horstmann  15 , Niels Harving  16 , Astrid Christine Petersen  17 , M Luz Calle  18 , Ewout W Steyerberg  19 , Willemien Beukers  20 , Kim E M van Kessel  20 , Jørgen Bjerggaard Jensen  8 , Jakob Skou Pedersen  1 , Per-Uno Malmström  6 , Núria Malats  5 , Francisco X Real  21 , Ellen C Zwarthoff  20 , Torben Falck Ørntoft  1 , Lars Dyrskjøt  22
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Free article

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Jakob Hedegaard et al. Cancer Cell. .
Free article

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.

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