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A Consensus Molecular Classification of Muscle-Invasive Bladder Cancer

63 Pages Posted: 19 Apr 2019 Publication Status: Review Complete

See all articles by Aurélie Kamoun

Aurélie Kamoun

French League Against Cancer - Tumor Identity Cards Program

Aurélien de Reyniès

French League Against Cancer - Tumor Identity Cards Program

Yves Allory

Institut Curie Hospital Group - Department of Pathology

Gottfrid Sjödahl

Lund University - Division of Urological Research

A. Gordon Robertson

Canada's Michael Smith Genome Sciences Center

Roland Seiler

University of Bern - Department of Urology

Katherine A. Hoadley

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

Hikmat Al-Ahmadie

Memorial Sloan Kettering Cancer Center - Department of Pathology

Woonyoung Choi

Johns Hopkins University - Greenberg Bladder Cancer Institute

Clarice S. Groeneveld

Federal University of Parana (UFPR) - Bioinformatics and Systems Biology Laboratory

Mauro A. A. Castro

Federal University of Parana (UFPR) - Bioinformatics and Systems Biology Laboratory

Jacqueline Fontugne

Institut Curie Hospital Group - Department of Pathology

Pontus Eriksson

Lund University - Division of Oncology and Pathology

Qianxing Mo

Baylor University - Department of Medicine

Jordan Kardos

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

Alexandre Zlotta

University of Toronto - Division of Urology

Arndt Hartmann

Friedrich-Alexander-Universität Erlangen-Nürnberg

Colin P. Dinney

University of Texas at Houston - Department of Urology; University of Texas at Houston - Department of Cancer Biology

Joaquim Bellmunt

Harvard Medical School - Bladder Cancer Center

Thomas Powles

Queen Mary University of London - Centre for Experimental Cancer Medicine

Núria Malats

Spanish National Cancer Research Centre (CNIO) - Genetic and Molecular Epidemiology Group

Keith S. Chan

Baylor University - Department of Molecular and Cellular Biology

William Y. Kim

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

David J. McConkey

Johns Hopkins University - Greenberg Bladder Cancer Institute

Peter C. Black

University of British Columbia (UBC) - Department of Urologic Sciences

Lars Dyrskjøt

Aarhus University Hospital - Department of Molecular Medicine

Mattias Höglund

Lund University - Division of Oncology and Pathology

Seth P. Lerner

Baylor University - Scott Department of Urology

Francisco X. Real

Spanish National Cancer Research Centre (CNIO) - Epithelial Carcinogenesis Group

François Radvanyi

Institut Curie - Molecular Oncology

The Bladder Cancer Molecular Taxonomy Group

Independent

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Abstract

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.

Suggested Citation

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.

Aurélie Kamoun (Contact Author)

French League Against Cancer - Tumor Identity Cards Program ( email )

France

Aurélien De Reyniès

French League Against Cancer - Tumor Identity Cards Program

France

Yves Allory

Institut Curie Hospital Group - Department of Pathology

France

Gottfrid Sjödahl

Lund University - Division of Urological Research

Sweden

A. Gordon Robertson

Canada's Michael Smith Genome Sciences Center

Canada

Roland Seiler

University of Bern - Department of Urology

Switzerland

Katherine A. Hoadley

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

United States

Hikmat Al-Ahmadie

Memorial Sloan Kettering Cancer Center - Department of Pathology

New York, NY
United States

Woonyoung Choi

Johns Hopkins University - Greenberg Bladder Cancer Institute

Baltimore, MD 20036-1984
United States

Clarice S. Groeneveld

Federal University of Parana (UFPR) - Bioinformatics and Systems Biology Laboratory

Brazil

Mauro A. A. Castro

Federal University of Parana (UFPR) - Bioinformatics and Systems Biology Laboratory

Brazil

Jacqueline Fontugne

Institut Curie Hospital Group - Department of Pathology

France

Pontus Eriksson

Lund University - Division of Oncology and Pathology

Sweden

Qianxing Mo

Baylor University - Department of Medicine

United States

Jordan Kardos

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

United States

Alexandre Zlotta

University of Toronto - Division of Urology

Canada

Arndt Hartmann

Friedrich-Alexander-Universität Erlangen-Nürnberg

Lange Gasse 20
Lange Gasse 20,
Nürnberg, 90403
Germany

Colin P. Dinney

University of Texas at Houston - Department of Urology

1515 Holcombe Blvd
Houston, TX 77230-1402
United States

University of Texas at Houston - Department of Cancer Biology

TX
United States

Joaquim Bellmunt

Harvard Medical School - Bladder Cancer Center

United States

Thomas Powles

Queen Mary University of London - Centre for Experimental Cancer Medicine

London
United Kingdom

Núria Malats

Spanish National Cancer Research Centre (CNIO) - Genetic and Molecular Epidemiology Group

Spain

Keith S. Chan

Baylor University - Department of Molecular and Cellular Biology

Houston, TX
United States

William Y. Kim

University of North Carolina (UNC) at Chapel Hill - Department of Genetics

United States

David J. McConkey

Johns Hopkins University - Greenberg Bladder Cancer Institute ( email )

Baltimore, MD 20036-1984
United States

Peter C. Black

University of British Columbia (UBC) - Department of Urologic Sciences

Canada

Lars Dyrskjøt

Aarhus University Hospital - Department of Molecular Medicine

Denmark

Mattias Höglund

Lund University - Division of Oncology and Pathology

Sweden

Seth P. Lerner

Baylor University - Scott Department of Urology

United States

Francisco X. Real

Spanish National Cancer Research Centre (CNIO) - Epithelial Carcinogenesis Group

Spain

François Radvanyi

Institut Curie - Molecular Oncology

France

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