A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.
Aurélie Kamoun,Aurélien de Reyniès,Yves Allory,Yves Allory,Gottfrid Sjödahl,A. Gordon Robertson,Roland Seiler,Katherine A. Hoadley,Clarice S. Groeneveld,Clarice S. Groeneveld,Hikmat Al-Ahmadie,Woonyoung Choi,Mauro A. A. Castro,Jacqueline Fontugne,Jacqueline Fontugne,Pontus Eriksson,Qianxing Mo,Jordan Kardos,Alexandre R. Zlotta,Arndt Hartmann,Colin Dinney,Joaquim Bellmunt,Thomas Powles,Núria Malats,Keith S. Chan,William Y. Kim,David J. McConkey,Peter C. Black,Lars Dyrskjøt,Mattias Höglund,Seth P. Lerner,Francisco X. Real,François Radvanyi,Mattias Aine,Isabelle Bernard-Pierrot,Bogdan Czerniak,Ewan A. Gibb,Jaegil Kim,David J. Kwiatkowski,Thierry Lebret,Fredrik Liedberg,Arlene O. Siefker-Radtke,Nanor Sirab,Ann Taber,John N. Weinstein +44 more
TLDR
In this paper, a consensus set of six molecular classes (luminal papillary (24%), luminal nonspecified (8), luminal unstable (15), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%) was identified.About:
This article is published in European Urology.The article was published on 2020-04-01 and is currently open access. It has received 629 citations till now.read more
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Journal ArticleDOI
European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines
J. Alfred Witjes,H.M. Bruins,Richard Cathomas,Eva Compérat,Nigel C. Cowan,Georgios Gakis,Virginia Hernández,Estefania Linares Espinós,Anja Lorch,Yann Neuzillet,Mathieu Rouanne,George N. Thalmann,Erik Veskimäe,Maria J. Ribal,Antoine G. van der Heijden +14 more
TL;DR: The results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.
Journal ArticleDOI
Advances in bladder cancer biology and therapy
TL;DR: Recent developments in the molecular and translational aspects of bladder cancer biology are examined and their current or potential future clinical applications in the management of bladdercancer are discussed.
Journal ArticleDOI
Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma
Sylvie Job,Delphine Rapoud,Delphine Rapoud,Alexandre Dos Santos,Alexandre Dos Santos,Patrick Gonzalez,Patrick Gonzalez,Christophe Desterke,G. Pascal,G. Pascal,Nabila Elarouci,Mira Ayadi,René Adam,René Adam,Daniel Azoulay,Daniel Azoulay,Denis Castaing,Denis Castaing,Eric Vibert,Eric Vibert,Daniel Cherqui,Daniel Cherqui,Didier Samuel,Didier Samuel,Antonio Sa Cuhna,Antonio Sa Cuhna,Agnès Marchio,Pascal Pineau,Catherine Guettier,Catherine Guettier,Aurélien de Reyniès,Jamila Faivre,Jamila Faivre +32 more
TL;DR: The heterogeneous tumor stroma composition is investigated and a TME‐based classification of ICC tumors that detects potentially targetable ICC subtypes is built.
Journal ArticleDOI
Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer.
Jiao Hu,Anze Yu,Anze Yu,Belaydi Othmane,Dongxu Qiu,Huihuang Li,Chao Li,Peihua Liu,Wenbiao Ren,Minfeng Chen,Guanghui Gong,Xi Guo,Huihui Zhang,Jinbo Chen,Xiongbing Zu +14 more
TL;DR: In this paper, the role of anti-Siglec15 in predicting the molecular subtype and the response to several treatment options in BLCA was analyzed using RNA sequencing data obtained from The Cancer Genome Atlas.
Journal ArticleDOI
An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.
Sia Viborg Lindskrog,Sia Viborg Lindskrog,Frederik Prip,Frederik Prip,Philippe Lamy,Ann Taber,Ann Taber,Clarice S. Groeneveld,Karin Birkenkamp-Demtröder,Karin Birkenkamp-Demtröder,Jørgen Bjerggaard Jensen,Jørgen Bjerggaard Jensen,Trine Strandgaard,Trine Strandgaard,Iver Nordentoft,Emil Christensen,Emil Christensen,Mateo Sokac,Mateo Sokac,Nicolai Juul Birkbak,Nicolai Juul Birkbak,Lasse Maretty,Lasse Maretty,Gregers G. Hermann,Astrid Christine Petersen,Veronika Weyerer,Marc-Oliver Grimm,Marcus Horstmann,Gottfrid Sjödahl,Mattias Höglund,Torben Steiniche,Karin Mogensen,Aurélien de Reyniès,Roman Nawroth,Brian J. Jordan,Xiaoqi Lin,Dejan Dragicevic,Douglas G. Ward,Anshita Goel,Carolyn D. Hurst,Jay D. Raman,Joshua I. Warrick,Ulrika Segersten,Danijel Sikic,Kim E.M. van Kessel,Tobias Maurer,Tobias Maurer,Joshua J. Meeks,David J. DeGraff,Richard T. Bryan,Margaret A. Knowles,Tatjana Simic,Arndt Hartmann,Ellen C. Zwarthoff,Per-Uno Malmström,Núria Malats,Francisco X. Real,Lars Dyrskjøt,Lars Dyrskjøt +58 more
Abstract: The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
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Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial
Jonathan E. Rosenberg,Jean H. Hoffman-Censits,Thomas Powles,Michiel S. van der Heijden,Arjun Vasant Balar,Andrea Necchi,Nancy A. Dawson,Peter H. O'Donnell,Ani Balmanoukian,Yohann Loriot,Sandy Srinivas,Margitta Retz,Petros Grivas,Richard W. Joseph,Matthew D. Galsky,Mark D. Fleming,Daniel P. Petrylak,Jose Luis Perez-Gracia,Howard A. Burris,Daniel Castellano,Christina Canil,Joaquim Bellmunt,Dean F. Bajorin,Dorothee Nickles,Richard Bourgon,Garrett M. Frampton,Na Cui,Sanjeev Mariathasan,Oyewale O. Abidoye,Gregg Fine,Robert Dreicer +30 more
TL;DR: Treatment with atezolizumab resulted in a significantly improved RECIST v1.1 response rate, compared with a historical control overall response rate of 10%, and Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolediazepine.
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Sanjeev Mariathasan,Shannon J. Turley,Dorothee Nickles,Alessandra Castiglioni,Kobe C. Yuen,Yulei Wang,Edward E. Kadel,Hartmut Koeppen,Jillian L. Astarita,Rafael Cubas,Suchit Jhunjhunwala,Romain Banchereau,Yagai Yang,Yinghui Guan,Cecile Chalouni,James Ziai,Yasin Senbabaoglu,Stephen Santoro,Daniel Sheinson,Jeffrey Hung,Jennifer M. Giltnane,Andrew A. Pierce,Kathryn Mesh,Steve Lianoglou,Johannes Riegler,Richard A.D. Carano,Pontus Eriksson,Mattias Höglund,Loan Somarriba,Daniel L. Halligan,Michiel S. van der Heijden,Yohann Loriot,Jonathan E. Rosenberg,Lawrence Fong,Ira Mellman,Daniel S. Chen,Marjorie C. Green,Christina Louise Derleth,Gregg Fine,Priti S. Hegde,Richard Bourgon,Thomas Powles +41 more
TL;DR: Tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent were examined and major determinants of clinical outcome were identified and suggested that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
Journal ArticleDOI
Comprehensive molecular characterization of urothelial bladder carcinoma
John N. Weinstein,Rehan Akbani,Bradley M. Broom,Wenyi Wang,Roeland Verhaak,David J. McConkey,Seth P. Lerner,Margaret Morgan,Chad J. Creighton,Carolyn L. Smith,Andrew D. Cherniack,Jaegil Kim,Chandra Sekhar Pedamallu,Michael S. Noble,Hikmat Al-Ahmadie,Victor E. Reuter,Jonathan E. Rosenberg,Dean F. Bajorin,Bernard H. Bochner,David B. Solit,Theresa M. Koppie,Brian D. Robinson,Dmitry A. Gordenin,David C. Fargo,Leszek J. Klimczak,Steven A. Roberts,Jessie Au,Peter W. Laird,Toshinori Hinoue,Nikolaus Schultz,Ricardo Ramirez,Donna E. Hansel,Katherine A. Hoadley,William Y. Kim,Jeffrey S. Damrauer,Stephen B. Baylin,Andrew J. Mungall,A. Gordon Robertson,Andy Chu,David J. Kwiatkowski,Carrie Sougnez,Kristian Cibulskis,Lee Lichtenstein,Andrey Sivachenko,Chip Stewart,Michael S. Lawrence,Gad Getz,Eric S. Lander,Stacey B. Gabrie,Lawrence A. Donehower,Scott L. Carter,Gordon Saksena,Steven E. Schumacher,Samuel S. Freeman,Joonil Jung,Ami S. Bhatt,Trevor J. Pugh,Rameen Beroukhim,Matthew Meyerson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Noreen Dhalla,Carrie Hirst,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Jacqueline E. Schein,Payal Sipahimalani,Angela Tam,Nina Thiessen,Tina Wong,Natasja Wye,Reanne Bowlby,Eric Chuah,Ranabir Guin,Hui Shen,Moiz S. Bootwalla,Timothy J. Triche,Phillip H. Lai,David Van Den Berg,Daniel J. Weisenberger,Saianand Balu,Tom Bodenheimer,Alan P. Hoyle,Stuart R. Jefferys,Shaowu Meng,Lisle E. Mose,Janae V. Simons,Mathew G. Soloway,Junyuan Wu,Joel S. Parker,D. Neil Hayes,Jeffrey Roach,Elizabeth Buda,Corbin D. Jones,Piotr A. Mieczkowski,Donghui Tan,Umadevi Veluvolu,Scot Waring,J. Todd Auman,Charles M. Perou,Matthew D. Wilkerson,Netty Santoso,Michael Parfenov,Xiaojia Ren,Angeliki Pantazi,Angela Hadjipanayis,Jonathan G. Seidman,Raju Kucherlapati,Semin Lee,Lixing Yang,Peter J. Park,Andrew Wei Xu,Alexei Protopopov,Jianhua Zhang,Christopher A. Bristow,Harshad S. Mahadeshwar,Sahil Seth,Xingzhi Song,Jiabin Tang,Dong Zeng,Lynda Chin,Lynda Chin,Charles C. Guo,Tod D. Casasent,Wenbin Liu,Zhenlin Ju,Thomas C. Motter,Bo Peng,Michael Ryan,Xiaoping Su,Ji Yeon Yang,Philip L. Lorenzi,Hui Yao,Nianxiang Zhang,Jiexin Zhang,Gordon B. Mills,Juok Cho,Daniel DiCara,Scott Frazer,Nils Gehlenborg,David I. Heiman,Pei Lin,Yingchun Liu,Petar Stojanov,Doug Voet,Hailei Zhang,Lihua Zou,Brady Bernard,Dick Kreisberg,Sheila Reynolds,Hector Rovira,Ilya Shmulevich,Jianjiong Gao,Anders Jacobsen,B. Arman Aksoy,Yevgeniy Antipin,Giovanni Ciriello,Gideon Dresdner,Benjamin Gross,William Lee,Boris Reva,Ronglai Shen,Rileen Sinha,S. Onur Sumer,Nils Weinhold,Marc Ladanyi,Chris Sander,Christopher C. Benz,Daniel E. Carlin,David Haussler,Sam Ng,Evano Paull,Joshua M. Stuart,Jing Zhu,Yuexin Liu,Wei Zhang,Barry S. Taylor,Tara M. Lichtenberg,Erik Zmuda,Thomas Barr,Aaron D. Black,Myra M. George,Benjamin Hanf,Carmen Helsel,Cynthia McAllister,Nilsa C. Ramirez,Nilsa C. Ramirez,Teresa R. Tabler,Stephanie Weaver,Lisa Wise,Jay Bowen,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Weiguo Jian,Sebrina A Tello,Michael Ittman,Patricia Castro,Whitney D. McClenden,Richard A. Gibbs,Charles Saller,Katherine Tarvin,Jennifer DiPiero,Jennifer Owens,Roni J. Bollag,Qiang Li,Paul M. Weinberger,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Pat Swanson,Troy Shelton,Erin Curley,Johanna Gardner,David Mallery,Robert Penny,Nguyen Van Bang,Phan Thi Hanh,Bernard Kohl,Xuan Van Le,Bui Duc Phu,Richard Thorp,Nguyen Viet Tien,Le Quang Vinh,George E. Sandusky,Eric J. Burks,Kimberly R. Christ,Jason R. Gee,Antonia H. Holway,Alireza Moinzadeh,Andrea Sorcini,Travis Sullivan,Ilana Rebecca Garcia-Grossman,Ashley Marie Regazzi,Lori Boice,W.K. Rathmell,Leigh B. Thorne,Sheldon I. Bastacky,Benjamin Davies,Rajiv Dhir,Jeffrey R. Gingrich,Ronald L. Hrebinko,Jodi K. Maranchie,Joel B. Nelson,Anil V. Parwani,Wiam Bshara,Carmelo Gaudioso,Carl Morrison,Vina Alexopoulou,John M. S. Bartlett,Jay Engel,Sugy Kodeeswaran,Tatjana Antic,Peter H. O'Donnell,Norm D. Smith,Gary D. Steinberg,Sophie C. Egea,Carmen Gomez-Fernandez,Lynn M. Herbert,Merce Jorda,Mark S. Soloway,Allison Beaver,Suzie Carter,Payal Kapur,Cheryl M. Lewis,Yair Lotan,Jolanta Bondaruk,Bogdan Czerniak,Eila C. Skinner,Kenneth Aldape,Mark A. Jensen,Ari B. Kahn,Todd Pihl,David Pot,Deepak Srinivasan,Yunhu Wan,Martin L. Ferguson,Jean C. Zenklusen,Tanja Davidsen,John A. Demchok,Kenna R. Mills Shaw,Kenna R. Mills Shaw,Margi Sheth,Roy Tarnuzzer,Zhining Wang,Liming Yang,Carolyn M. Hutter,Bradley A. Ozenberger,Heidi J. Sofia,Greg Eley +296 more
TL;DR: Ch Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
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Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial
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TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
Sanjeev Mariathasan,Shannon J. Turley,Dorothee Nickles,Alessandra Castiglioni,Kobe C. Yuen,Yulei Wang,Edward E. Kadel,Hartmut Koeppen,Jillian L. Astarita,Rafael Cubas,Suchit Jhunjhunwala,Romain Banchereau,Yagai Yang,Yinghui Guan,Cecile Chalouni,James Ziai,Yasin Senbabaoglu,Stephen Santoro,Daniel Sheinson,Jeffrey Hung,Jennifer M. Giltnane,Andrew A. Pierce,Kathryn Mesh,Steve Lianoglou,Johannes Riegler,Richard A.D. Carano,Pontus Eriksson,Mattias Höglund,Loan Somarriba,Daniel L. Halligan,Michiel S. van der Heijden,Yohann Loriot,Jonathan E. Rosenberg,Lawrence Fong,Ira Mellman,Daniel S. Chen,Marjorie C. Green,Christina Louise Derleth,Gregg Fine,Priti S. Hegde,Richard Bourgon,Thomas Powles +41 more