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dc.date.accessioned2018-03-20T13:59:20Z
dc.date.available2018-03-20T13:59:20Z
dc.date.created2017-10-12T12:25:23Z
dc.date.issued2017
dc.identifier.citationUrbanucci, Alfonso Barfeld, Stefan Jörg Kytölä, Ville Itkonen, Harri Coleman, Ilsa M. Vodák, Daniel Sjöblom, Liisa Sheng, Xia Minner, Sarah Burdelski, Christoph Kivinummi, Kati K. Kohvakka, Annika Kregel, Steven Takhar, Mandeep Alshalalfa, Mohammed Davicioni, Elai Erho, Nicholas Lloyd, Paul Karnes, R. Jeffrey Ross, Ashley E. Schaeffer, Edward M. Vander Griend, Donald J Knapp, Stefan Corey, Eva Feng, Felix Y. Nelson, Peter S. Saatcioglu, Fahri Knudsen, Karen E. Tammela, Teuvo L.J. Sauter, Guido Schlomm, Thorsten Nykter, Matti Visakorpi, Tapio Mills, Ian Geoffrey . Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer. Cell reports. 2017, 19(10), 2045-2059
dc.identifier.urihttp://hdl.handle.net/10852/61183
dc.description.abstractGlobal changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.en_US
dc.languageEN
dc.language.isoenen_US
dc.publisherCell Press
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleAndrogen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate canceren_US
dc.typeJournal articleen_US
dc.creator.authorUrbanucci, Alfonso
dc.creator.authorBarfeld, Stefan Jörg
dc.creator.authorKytölä, Ville
dc.creator.authorItkonen, Harri
dc.creator.authorColeman, Ilsa M.
dc.creator.authorVodák, Daniel
dc.creator.authorSjöblom, Liisa
dc.creator.authorSheng, Xia
dc.creator.authorMinner, Sarah
dc.creator.authorBurdelski, Christoph
dc.creator.authorKivinummi, Kati K.
dc.creator.authorKohvakka, Annika
dc.creator.authorKregel, Steven
dc.creator.authorTakhar, Mandeep
dc.creator.authorAlshalalfa, Mohammed
dc.creator.authorDavicioni, Elai
dc.creator.authorErho, Nicholas
dc.creator.authorLloyd, Paul
dc.creator.authorKarnes, R. Jeffrey
dc.creator.authorRoss, Ashley E.
dc.creator.authorSchaeffer, Edward M.
dc.creator.authorVander Griend, Donald J
dc.creator.authorKnapp, Stefan
dc.creator.authorCorey, Eva
dc.creator.authorFeng, Felix Y.
dc.creator.authorNelson, Peter S.
dc.creator.authorSaatcioglu, Fahri
dc.creator.authorKnudsen, Karen E.
dc.creator.authorTammela, Teuvo L.J.
dc.creator.authorSauter, Guido
dc.creator.authorSchlomm, Thorsten
dc.creator.authorNykter, Matti
dc.creator.authorVisakorpi, Tapio
dc.creator.authorMills, Ian Geoffrey
cristin.unitcode185,57,11,0
cristin.unitnameMills/Engedal Group - Prostate Cancer
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.fulltextpostprint
cristin.qualitycode1
dc.identifier.cristin1504115
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cell reports&rft.volume=19&rft.spage=2045&rft.date=2017
dc.identifier.jtitleCell reports
dc.identifier.volume19
dc.identifier.issue10
dc.identifier.startpage2045
dc.identifier.endpage2059
dc.identifier.doihttp://dx.doi.org/10.1016/j.celrep.2017.05.049
dc.identifier.urnURN:NBN:no-63816
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2211-1247
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/61183/5/1-s2.0-S2211124717307064-mmc9.pdf
dc.type.versionPublishedVersion


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