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

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dc.citation.articleNumber101201en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitleiScienceen_US
dc.citation.volumeNumber23en_US
dc.contributor.authorYang, Guoliangen_US
dc.contributor.authorBondaruk, Jolantaen_US
dc.contributor.authorCogdell, Daviden_US
dc.contributor.authorWang, Ziqiaoen_US
dc.contributor.authorLee, Sangkyouen_US
dc.contributor.authorLee, June Gooen_US
dc.contributor.authorZhang, Shizhenen_US
dc.contributor.authorChoi, Woonyoungen_US
dc.contributor.authorWang, Yanen_US
dc.contributor.authorLiang, Yuen_US
dc.contributor.authorWang, Gangen_US
dc.contributor.authorWang, Yingen_US
dc.contributor.authorYao, Huien_US
dc.contributor.authorDadhania, Vipulkumaren_US
dc.contributor.authorGao, Jianjunen_US
dc.contributor.authorLogothetis, Christopheren_US
dc.contributor.authorSiefker-Radtke, Arleneen_US
dc.contributor.authorKamat, Ashishen_US
dc.contributor.authorDinney, Colinen_US
dc.contributor.authorTheodorescu, Danen_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorWei, Pengen_US
dc.contributor.authorGuo, Charles C.en_US
dc.contributor.authorWeinstein, John N.en_US
dc.contributor.authorMcConkey, David J.en_US
dc.contributor.authorCzerniak, Bogdanen_US
dc.date.accessioned2020-10-30T19:43:45Zen_US
dc.date.available2020-10-30T19:43:45Zen_US
dc.date.issued2020en_US
dc.description.abstractWe 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.en_US
dc.identifier.citationYang, Guoliang, Bondaruk, Jolanta, Cogdell, David, et al.. "Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer." <i>iScience,</i> 23, no. 6 (2020) Cell Press: https://doi.org/10.1016/j.isci.2020.101201.en_US
dc.identifier.doihttps://doi.org/10.1016/j.isci.2020.101201en_US
dc.identifier.urihttps://hdl.handle.net/1911/109466en_US
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleUrothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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