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Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer

We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer Genome Atlas cohort of 408 conventional UC bladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly u...

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Autores principales: Yang, Guoliang, Bondaruk, Jolanta, Cogdell, David, Wang, Ziqiao, Lee, Sangkyou, Lee, June Goo, Zhang, Shizhen, Choi, Woonyoung, Wang, Yan, Liang, Yu, Wang, Gang, Wang, Ying, Yao, Hui, Dadhania, Vipulkumar, Gao, Jianjun, Logothetis, Christopher, Siefker-Radtke, Arlene, Kamat, Ashish, Dinney, Colin, Theodorescu, Dan, Kimmel, Marek, Wei, Peng, Guo, Charles C., Weinstein, John N., McConkey, David J., Czerniak, Bogdan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286965/
https://www.ncbi.nlm.nih.gov/pubmed/32521509
http://dx.doi.org/10.1016/j.isci.2020.101201
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author Yang, Guoliang
Bondaruk, Jolanta
Cogdell, David
Wang, Ziqiao
Lee, Sangkyou
Lee, June Goo
Zhang, Shizhen
Choi, Woonyoung
Wang, Yan
Liang, Yu
Wang, Gang
Wang, Ying
Yao, Hui
Dadhania, Vipulkumar
Gao, Jianjun
Logothetis, Christopher
Siefker-Radtke, Arlene
Kamat, Ashish
Dinney, Colin
Theodorescu, Dan
Kimmel, Marek
Wei, Peng
Guo, Charles C.
Weinstein, John N.
McConkey, David J.
Czerniak, Bogdan
author_facet Yang, Guoliang
Bondaruk, Jolanta
Cogdell, David
Wang, Ziqiao
Lee, Sangkyou
Lee, June Goo
Zhang, Shizhen
Choi, Woonyoung
Wang, Yan
Liang, Yu
Wang, Gang
Wang, Ying
Yao, Hui
Dadhania, Vipulkumar
Gao, Jianjun
Logothetis, Christopher
Siefker-Radtke, Arlene
Kamat, Ashish
Dinney, Colin
Theodorescu, Dan
Kimmel, Marek
Wei, Peng
Guo, Charles C.
Weinstein, John N.
McConkey, David J.
Czerniak, Bogdan
author_sort Yang, Guoliang
collection PubMed
description We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer Genome Atlas cohort of 408 conventional UC bladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly uniform inactivation of TP53 and were dominated by Sanger mutation signature 3 associated with loss of BRCA1/2 function. SCCs were characterized by downregulation of luminal and basal markers and were referred to as double-negative. Transcriptome analyses indicated that SCCs displayed lineage plasticity driven by a urothelial-to-neural phenotypic switch with a dysregulated epithelial-to-mesenchymal transition network. SCCs were depleted of immune cells, and expressed high levels of the immune checkpoint receptor, adenosine receptor A2A (ADORA2A), which is a potent inhibitor of immune infiltration. Our observations have important implications for the prognostication and development of more effective therapies for this lethal bladder cancer variant.
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spelling pubmed-72869652020-06-15 Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer Yang, Guoliang Bondaruk, Jolanta Cogdell, David Wang, Ziqiao Lee, Sangkyou Lee, June Goo Zhang, Shizhen Choi, Woonyoung Wang, Yan Liang, Yu Wang, Gang Wang, Ying Yao, Hui Dadhania, Vipulkumar Gao, Jianjun Logothetis, Christopher Siefker-Radtke, Arlene Kamat, Ashish Dinney, Colin Theodorescu, Dan Kimmel, Marek Wei, Peng Guo, Charles C. Weinstein, John N. McConkey, David J. Czerniak, Bogdan iScience Article We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer Genome Atlas cohort of 408 conventional UC bladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly uniform inactivation of TP53 and were dominated by Sanger mutation signature 3 associated with loss of BRCA1/2 function. SCCs were characterized by downregulation of luminal and basal markers and were referred to as double-negative. Transcriptome analyses indicated that SCCs displayed lineage plasticity driven by a urothelial-to-neural phenotypic switch with a dysregulated epithelial-to-mesenchymal transition network. SCCs were depleted of immune cells, and expressed high levels of the immune checkpoint receptor, adenosine receptor A2A (ADORA2A), which is a potent inhibitor of immune infiltration. Our observations have important implications for the prognostication and development of more effective therapies for this lethal bladder cancer variant. Elsevier 2020-05-27 /pmc/articles/PMC7286965/ /pubmed/32521509 http://dx.doi.org/10.1016/j.isci.2020.101201 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yang, Guoliang
Bondaruk, Jolanta
Cogdell, David
Wang, Ziqiao
Lee, Sangkyou
Lee, June Goo
Zhang, Shizhen
Choi, Woonyoung
Wang, Yan
Liang, Yu
Wang, Gang
Wang, Ying
Yao, Hui
Dadhania, Vipulkumar
Gao, Jianjun
Logothetis, Christopher
Siefker-Radtke, Arlene
Kamat, Ashish
Dinney, Colin
Theodorescu, Dan
Kimmel, Marek
Wei, Peng
Guo, Charles C.
Weinstein, John N.
McConkey, David J.
Czerniak, Bogdan
Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title_full Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title_fullStr Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title_full_unstemmed Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title_short Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer
title_sort urothelial-to-neural plasticity drives progression to small cell bladder cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286965/
https://www.ncbi.nlm.nih.gov/pubmed/32521509
http://dx.doi.org/10.1016/j.isci.2020.101201
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