Journal
CANCER CELL
Volume 30, Issue 1, Pages 27-42Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2016.05.004
Keywords
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Categories
Funding
- John and Birthe Meyer Foundation
- Danish Research Council for Independent Research
- Lundbeck Foundation
- Danish Cancer Biobank
- Danish Cancer Society
- Spanish Ministry of Economy [MTM2012-38067-C02-02]
- Consolider ONCOBIO from MINECO (Madrid, Spain)
- RTICC (Instituto de Salud Carlos III, Madrid, Spain) [RD12/0036/0034]
- EU-FP7 [201663]
- RTICC-ISCIII [RD12/0036/0050]
- [EU-FP7-HEALTH-F2-2008]
- [201333]
- [EU-FP7-HEALTH-F5-2013]
- [601933]
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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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