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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Hedegaard, Jakob ; Lamy, Philippe ; Nordentoft, Iver ; Algaba, Ferran ; Høyer, Søren ; Ulhøi, Benedicte Parm ; Vang, Søren ; Reinert, Thomas ; Hermann, Gregers G. and Mogensen, Karin , et al. (2016) In Cancer Cell 30(1). p.27-42
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
30
issue
1
pages
16 pages
publisher
Cell Press
external identifiers
  • wos:000380077100010
  • pmid:27321955
  • scopus:84979732333
ISSN
1535-6108
DOI
10.1016/j.ccell.2016.05.004
language
English
LU publication?
yes
id
e6a8b65c-c749-48c0-9891-982d1716246f
date added to LUP
2016-08-16 16:16:57
date last changed
2025-03-09 17:45:09
@article{e6a8b65c-c749-48c0-9891-982d1716246f,
  abstract     = {{<p>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.</p>}},
  author       = {{Hedegaard, Jakob and Lamy, Philippe and Nordentoft, Iver and Algaba, Ferran and Høyer, Søren and Ulhøi, Benedicte Parm and Vang, Søren and Reinert, Thomas and Hermann, Gregers G. and Mogensen, Karin and Thomsen, Mathilde Borg Houlberg and Nielsen, Morten Muhlig and Marquez, Mirari and Segersten, Ulrika and Aine, Mattias and Höglund, Mattias and Birkenkamp-Demtröder, Karin and Fristrup, Niels and Borre, Michael and Hartmann, Arndt and Stöhr, Robert and Wach, Sven and Keck, Bastian and Seitz, Anna Katharina and Nawroth, Roman and Maurer, Tobias and Tulic, Cane and Simic, Tatjana and Junker, Kerstin and Horstmann, Marcus and Harving, Niels and Petersen, Astrid Christine and Calle, M. Luz and Steyerberg, Ewout W. and Beukers, Willemien and van Kessel, Kim E M and Jensen, Jørgen Bjerggaard and Pedersen, Jakob Skou and Malmström, Per Uno and Malats, Núria and Real, Francisco X. and Zwarthoff, Ellen C. and Ørntoft, Torben Falck and Dyrskjøt, Lars}},
  issn         = {{1535-6108}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  pages        = {{27--42}},
  publisher    = {{Cell Press}},
  series       = {{Cancer Cell}},
  title        = {{Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma}},
  url          = {{http://dx.doi.org/10.1016/j.ccell.2016.05.004}},
  doi          = {{10.1016/j.ccell.2016.05.004}},
  volume       = {{30}},
  year         = {{2016}},
}