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Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

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Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer. / Urbanucci, Alfonso; Barfeld, Stefan J.; Kytölä, Ville; Itkonen, Harri M.; Coleman, Ilsa M.; Vodák, Daniel; Sjöblom, Liisa; Sheng, Xia; Tolonen, Teemu; 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 G.

In: Cell Reports, Vol. 19, No. 10, 06.06.2017, p. 2045-2059.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Urbanucci, A, Barfeld, SJ, Kytölä, V, Itkonen, HM, Coleman, IM, Vodák, D, Sjöblom, L, Sheng, X, Tolonen, T, Minner, S, Burdelski, C, Kivinummi, KK, Kohvakka, A, Kregel, S, Takhar, M, Alshalalfa, M, Davicioni, E, Erho, N, Lloyd, P, Karnes, RJ, Ross, AE, Schaeffer, EM, Vander Griend, DJ, Knapp, S, Corey, E, Feng, FY, Nelson, PS, Saatcioglu, F, Knudsen, KE, Tammela, TLJ, Sauter, G, Schlomm, T, Nykter, M, Visakorpi, T & Mills, IG 2017, 'Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer', Cell Reports, vol. 19, no. 10, pp. 2045-2059. https://doi.org/10.1016/j.celrep.2017.05.049

APA

Urbanucci, A., Barfeld, S. J., Kytölä, V., Itkonen, H. M., Coleman, I. M., Vodák, D., ... Mills, I. G. (2017). Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer. Cell Reports, 19(10), 2045-2059. https://doi.org/10.1016/j.celrep.2017.05.049

Vancouver

Urbanucci A, Barfeld SJ, Kytölä V, Itkonen HM, Coleman IM, Vodák D et al. Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer. Cell Reports. 2017 Jun 6;19(10):2045-2059. https://doi.org/10.1016/j.celrep.2017.05.049

Author

Urbanucci, Alfonso ; Barfeld, Stefan J. ; Kytölä, Ville ; Itkonen, Harri M. ; Coleman, Ilsa M. ; Vodák, Daniel ; Sjöblom, Liisa ; Sheng, Xia ; Tolonen, Teemu ; 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 G. / Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer. In: Cell Reports. 2017 ; Vol. 19, No. 10. pp. 2045-2059.

Bibtex - Download

@article{de710404696341918f2f12b785689ad8,
title = "Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer",
abstract = "Global 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.",
keywords = "androgen receptor, ATAD2, BRD2, BRD4, BROMO-10, bromodomain inhibitor, castration-resistant prostate cancer, chromatin",
author = "Alfonso Urbanucci and Barfeld, {Stefan J.} and Ville Kyt{\"o}l{\"a} and Itkonen, {Harri M.} and Coleman, {Ilsa M.} and Daniel Vod{\'a}k and Liisa Sj{\"o}blom and Xia Sheng and Teemu Tolonen and Sarah Minner and Christoph Burdelski and Kivinummi, {Kati K.} and Annika Kohvakka and Steven Kregel and Mandeep Takhar and Mohammed Alshalalfa and Elai Davicioni and Nicholas Erho and Paul Lloyd and Karnes, {R. Jeffrey} and Ross, {Ashley E.} and Schaeffer, {Edward M.} and {Vander Griend}, {Donald J.} and Stefan Knapp and Eva Corey and Feng, {Felix Y.} and Nelson, {Peter S.} and Fahri Saatcioglu and Knudsen, {Karen E.} and Tammela, {Teuvo L.J.} and Guido Sauter and Thorsten Schlomm and Matti Nykter and Tapio Visakorpi and Mills, {Ian G.}",
year = "2017",
month = "6",
day = "6",
doi = "10.1016/j.celrep.2017.05.049",
language = "English",
volume = "19",
pages = "2045--2059",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "10",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

AU - Urbanucci, Alfonso

AU - Barfeld, Stefan J.

AU - Kytölä, Ville

AU - Itkonen, Harri M.

AU - Coleman, Ilsa M.

AU - Vodák, Daniel

AU - Sjöblom, Liisa

AU - Sheng, Xia

AU - Tolonen, Teemu

AU - Minner, Sarah

AU - Burdelski, Christoph

AU - Kivinummi, Kati K.

AU - Kohvakka, Annika

AU - Kregel, Steven

AU - Takhar, Mandeep

AU - Alshalalfa, Mohammed

AU - Davicioni, Elai

AU - Erho, Nicholas

AU - Lloyd, Paul

AU - Karnes, R. Jeffrey

AU - Ross, Ashley E.

AU - Schaeffer, Edward M.

AU - Vander Griend, Donald J.

AU - Knapp, Stefan

AU - Corey, Eva

AU - Feng, Felix Y.

AU - Nelson, Peter S.

AU - Saatcioglu, Fahri

AU - Knudsen, Karen E.

AU - Tammela, Teuvo L.J.

AU - Sauter, Guido

AU - Schlomm, Thorsten

AU - Nykter, Matti

AU - Visakorpi, Tapio

AU - Mills, Ian G.

PY - 2017/6/6

Y1 - 2017/6/6

N2 - Global 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.

AB - Global 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.

KW - androgen receptor

KW - ATAD2

KW - BRD2

KW - BRD4

KW - BROMO-10

KW - bromodomain inhibitor

KW - castration-resistant prostate cancer

KW - chromatin

U2 - 10.1016/j.celrep.2017.05.049

DO - 10.1016/j.celrep.2017.05.049

M3 - Article

VL - 19

SP - 2045

EP - 2059

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 10

ER -