Muscle-Invasive Bladder Cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, yielding diverse sets of subtypes. This diversity hampers the clinical application of such knowledge. Here, we report the results of a large international effort to reach a consensus on MIBC molecular subtypes. Using 1750 MIBC transcriptomes and a network-based analysis of six independent MIBC classification systems, we identified a consensus set of six molecular classes: Luminal Papillary (24%), Luminal Non-Specified (8%), Luminal Unstable (15%), Stroma-rich (15%), Basal/Squamous (35%), and Neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics. This consensus system offers a robust framework that will enable testing and validating predictive biomarkers in future clinical trials.
Kamoun, Aurélie and de Reyniès, Aurélien and Allory, Yves and Sjödahl, Gottfrid and Robertson, A. Gordon and Seiler, Roland and Hoadley, Katherine A. and Al-Ahmadie, Hikmat and Choi, Woonyoung and Groeneveld, Clarice S. and Castro, Mauro A. A. and Fontugne, Jacqueline and Eriksson, Pontus and Mo, Qianxing and Kardos, Jordan and Zlotta, Alexandre and Hartmann, Arndt and Dinney, Colin P. and Bellmunt, Joaquim and Powles, Thomas and Malats, Núria and Chan, Keith S. and Kim, William Y. and McConkey, David J. and Black, Peter C. and Dyrskjøt, Lars and Höglund, Mattias and Lerner, Seth P. and Real, Francisco X. and Radvanyi, François and Group, The Bladder Cancer Molecular Taxonomy, A Consensus Molecular Classification of Muscle-Invasive Bladder Cancer (April 16, 2019). Available at SSRN: https://ssrn.com/abstract=3372965 or http://dx.doi.org/10.2139/ssrn.3372965
This version of the paper has not been formally peer reviewed.
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