Androgens2016 Oral Communications (1) (17 abstracts)
Chromatin relaxation is a feature of advanced prostate cancer
Alfonso Urbanucci 1, , Stefan Barfeld 1 , Ville Kytölä 3 , Daniel Vodák 4 , Liisa Sjöblom 5 , Teemu Tolonen 6 , Sarah Minner 7 , Christoph Burdelski 8 , Kati K. Kivinummi 3 , Steven Kregel 9, , Mandeep Takhar 11 , Mohammed Alshalalfa 11 , Elai Davicioni 11 , Nicholas Erho 11 , R. Jeffrey Karnes 12 , Ashley E. Ross 13 , Edward M. Schaeffer 13 , Donald J. Vander Griend 9 , Stefan Knapp 14, , Teuvo L.J. Tammela 16 , Guido Sauter 7 , Thorsten Schlomm 17 , Matti Nykter 3 , Tapio Visakorpi 5 & Ian G. Mills 1,
1Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Forksningsparken, University of Oslo, Oslo, Norway; 2Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; 3Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Tampere University of Technology, Tampere, Finland; 4Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 5Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere and Fimlab Laboratories, Tampere University Hospital, Tampere, Finland; 6Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland; 7University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 8General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 9Department of Surgery - Section of Urology, University of Chicago, Chicago, Illinois, USA; 10Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA; 11Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada, V6B 1B8; 12Department of Urology, Mayo Clinic, Rochester, MN, USA; 13Brady Urological Institute, Johns Hopkins Medical Institute, Baltimore, MD, USA; 14Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK; 15Institute for Pharmaceutical Chemistry, Goethe-University Frankfurt, Campus Riedberg, Max-von Laue Str. 9, 60438 Frankfurt am Main, Germany; 16Prostate Cancer Research Center and Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland; 17Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 18PCUK Movember Centre of Excellence, CCRCB, Queen’s University, Belfast, UK
Epigenetic reprogramming including altered transcription factor binding and altered patterns of chromatin and DNA modifications are now accepted as the hallmark of aggressive cancers. We show that global changes in chromatin structure and chromatin accessibility in prostate tumour tissue can define castrate-resistant prostate cancer and be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor overexpression alone, which is a hallmark of progression on its own, is a primary driver for chromatin relaxation, which can lead to promiscuous binding of other key transcription factors important to disease progression. We identify mediators of chromatin relaxation that can be used as disease biomarker and show that such mediators identify DNA stretches enriched in low p-value GWAS-significant disease/tissue-specific susceptibility loci.
Presenting Author: Urbanucci Alfonso Urbanucci, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, Forksningsparken, University of Oslo, Oslo, Norway and Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Email: [email protected]
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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