Kaulfuß, Silke

[["dc.bibliographiccitation.firstpage","1124"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Der Urologe"],["dc.bibliographiccitation.lastpage","1130"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Thelen, Paul"],["dc.contributor.author","Strauss, A."],["dc.contributor.author","Stettner, Mark"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Ringert, Rolf-Hermann"],["dc.contributor.author","Loertzer, Hagen"],["dc.date.accessioned","2018-11-07T08:40:13Z"],["dc.date.available","2018-11-07T08:40:13Z"],["dc.date.issued","2010"],["dc.description.abstract","In advanced prostate cancer, albeit castration resistant, an active androgen receptor is still pivotal for growth and cell survival. Recent therapies involving more effective antiandrogens such as MDV3100 proved to be successful. Furthermore, blocking de novo intracrine androgen synthesis, e.g. with abiraterone acetate, provides additional benefit. Besides these antiandrogen measures, compounds which enable the reconstitution of the oestrogen receptor beta as a tumour suppressor restrain aberrant androgen receptor signalling."],["dc.identifier.doi","10.1007/s00120-010-2370-0"],["dc.identifier.isi","000281611000003"],["dc.identifier.pmid","20725712"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7794"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19177"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1433-0563"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Antiandrogen strategies in prostate cancer Reconstitution of the beta-Ostrogenrezeptors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","593"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Histopathology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Filmar, Simon"],["dc.contributor.author","Gaisa, Nadine T"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Reis, Henning"],["dc.contributor.author","Nettersheim, Daniel"],["dc.contributor.author","Oing, Christoph"],["dc.contributor.author","Gayer, Fabian A"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Bremmer, Felix"],["dc.date.accessioned","2021-04-14T08:23:39Z"],["dc.date.available","2021-04-14T08:23:39Z"],["dc.date.issued","2020"],["dc.description.abstract","Aims Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so‐called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in‐situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time‐consuming, demanding, and not being a stand‐alone method. The aim of the present study was to establish a quantitative real‐time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin‐fixed paraffin‐embedded tissue. Methods and results A cut‐off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour‐free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p). Conclusion In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin."],["dc.description.sponsorship","Wilhelm Sander‐Stiftung http://dx.doi.org/10.13039/100008672"],["dc.identifier.doi","10.1111/his.14258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81003"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1365-2559"],["dc.relation.issn","0309-0167"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","The detection of isochromosome i(12p) in malignant germ cell tumours and tumours with somatic malignant transformation by the use of quantitative real‐time polymerase chain reaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Dumont, Martine; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Weber-Lassalle, Nana; 2Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; nana.weber-lassalle@uk-koeln.de (N.W.-L.); corinna.ernst@uk-koeln.de (C.E.); rita.schmutzler@uk-koeln.de (R.K.S.); eric.hahnen@uk-koeln.de (E.H.)"],["dc.contributor.affiliation","Joly-Beauparlant, Charles; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Ernst, Corinna; 2Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; nana.weber-lassalle@uk-koeln.de (N.W.-L.); corinna.ernst@uk-koeln.de (C.E.); rita.schmutzler@uk-koeln.de (R.K.S.); eric.hahnen@uk-koeln.de (E.H.)"],["dc.contributor.affiliation","Droit, Arnaud; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Feng, Bing-Jian; 3Department of Dermatology, University of Utah, Salt Lake City, UT 84103, USA; bingjian.feng@hsc.utah.edu (B.-J.F.); david.goldgar@hsc.utah.edu (D.E.G.)"],["dc.contributor.affiliation","Dubois, Stéphane; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Collin-Deschesnes, Annie-Claude; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Soucy, Penny; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Vallée, Maxime; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Fournier, Frédéric; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Lemaçon, Audrey; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.affiliation","Adank, Muriel A.; 5Family Cancer Clinic, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; m.adank@nki.nl (M.A.A.); f.hogervorst@nki.nl (F.B.L.H.); l.vd.kolk@nki.nl (L.v.d.K.)"],["dc.contributor.affiliation","Allen, Jamie; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Altmüller, Janine; 7Cologne Center for Genomics (CCG), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; janine.altmueller@mdc-berlin.de (J.A.); holger.thiele@uni-koeln.de (H.T.)"],["dc.contributor.affiliation","Arnold, Norbert; 8Institute of Clinical Molecular Biology, Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, 24105 Kiel, Germany; norbert.arnold@uksh.de"],["dc.contributor.affiliation","Ausems, Margreet G. E. M.; 9Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center Utrecht, 3584 Utrecht, The Netherlands; m.g.e.m.ausems@umcutrecht.nl"],["dc.contributor.affiliation","Berutti, Riccardo; 10Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany; riccardo.berutti@helmholtz-muenchen.de (R.B.); tim.strom@tum.de (T.M.S.)"],["dc.contributor.affiliation","Bolla, Manjeet K.; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Bull, Shelley; 11Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; bull@lunenfeld.ca (S.B.); jessica.green@sinaihealth.ca (J.G.); gary.bader@utoronto.ca (G.D.B.); andrulis@lunenfeld.ca (I.L.A.)"],["dc.contributor.affiliation","Carvalho, Sara; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Cornelissen, Sten; 13Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; s.cornelissen@nki.nl (S.C.); r.keeman@nki.nl (R.K.); mk.schmidt@nki.nl (M.K.S.)"],["dc.contributor.affiliation","Dufault, Michael R.; 14Precision Medicine and Computational Biology, Sanofi Genzyme, Cambridge, MA 02142, USA; michael.dufault@sanofi.com"],["dc.contributor.affiliation","Dunning, Alison M.; 15Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; amd24@medschl.cam.ac.uk (A.M.D.); craig@srl.cam.ac.uk (C.L.); ms483@medschl.cam.ac.uk (M.S.)"],["dc.contributor.affiliation","Engel, Christoph; 16Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany; christoph.engel@imise.uni-leipzig.de"],["dc.contributor.affiliation","Gehrig, Andrea; 17Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University of Würzburg, 97074 Würzburg, Germany; gehrig@biozentrum.uni-wuerzburg.de"],["dc.contributor.affiliation","Geurts-Giele, Willemina R. R.; 18Department of Clinical Genetics, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands; w.geurts-giele@erasmusmc.nl"],["dc.contributor.affiliation","Gieger, Christian; 19Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; christian.gieger@helmholtz-muenchen.de (C.G.); peters@helmholtz-muenchen.de (A.P.)"],["dc.contributor.affiliation","Green, Jessica; 11Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; bull@lunenfeld.ca (S.B.); jessica.green@sinaihealth.ca (J.G.); gary.bader@utoronto.ca (G.D.B.); andrulis@lunenfeld.ca (I.L.A.)"],["dc.contributor.affiliation","Hackmann, Karl; 22Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; karl.hackmann@uniklinikum-dresden.de"],["dc.contributor.affiliation","Helmy, Mohamed; 23The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; mohamed_helmy@bii.a-star.edu.sg"],["dc.contributor.affiliation","Hentschel, Julia; 26Institute of Human Genetics, University Leipzig, 04103 Leipzig, Germany; julia.hentschel@medizin.uni-leipzig.de"],["dc.contributor.affiliation","Hogervorst, Frans B. L.; 5Family Cancer Clinic, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; m.adank@nki.nl (M.A.A.); f.hogervorst@nki.nl (F.B.L.H.); l.vd.kolk@nki.nl (L.v.d.K.)"],["dc.contributor.affiliation","Hollestelle, Antoinette; 27Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands; a.hollestelle@erasmusmc.nl (A.H.); m.hooning@erasmusmc.nl (M.J.H.); j.martens@erasmusmc.nl (J.W.M.M.)"],["dc.contributor.affiliation","Hooning, Maartje J.; 27Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands; a.hollestelle@erasmusmc.nl (A.H.); m.hooning@erasmusmc.nl (M.J.H.); j.martens@erasmusmc.nl (J.W.M.M.)"],["dc.contributor.affiliation","Horváth, Judit; 28Institute of Human Genetics, University of Münster, 48149 Münster, Germany; judit.horvath@ukmuenster.de"],["dc.contributor.affiliation","Ikram, M. Arfan; 29Department of Epidemiology, Erasmus MC University Medical Center, 3015 Rotterdam, The Netherlands; m.a.ikram@erasmusmc.nl"],["dc.contributor.affiliation","Kaulfuß, Silke; 30Institute of Human Genetics, University Medical Center Göttingen, 37075 Göttingen, Germany; silke.kaulfuss@med.uni-goettingen.de"],["dc.contributor.affiliation","Keeman, Renske; 13Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; s.cornelissen@nki.nl (S.C.); r.keeman@nki.nl (R.K.); mk.schmidt@nki.nl (M.K.S.)"],["dc.contributor.affiliation","Kuang, Da; 21Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; kvn.kuang@mail.utoronto.ca"],["dc.contributor.affiliation","Luccarini, Craig; 15Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; amd24@medschl.cam.ac.uk (A.M.D.); craig@srl.cam.ac.uk (C.L.); ms483@medschl.cam.ac.uk (M.S.)"],["dc.contributor.affiliation","Maier, Wolfgang; 31German Center for Neurodegenerative Diseases (DZNE), Department of Neurodegenerative Diseases and Geriatric Psychiatry, Medical Faculty, University Hospital Bonn, 53127 Bonn, Germany; wolfgang.maier@ukb.uni-bonn.de"],["dc.contributor.affiliation","Martens, John W. M.; 27Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands; a.hollestelle@erasmusmc.nl (A.H.); m.hooning@erasmusmc.nl (M.J.H.); j.martens@erasmusmc.nl (J.W.M.M.)"],["dc.contributor.affiliation","Niederacher, Dieter; 32Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany; niederac@med.uni-duesseldorf.de"],["dc.contributor.affiliation","Nürnberg, Peter; 33Center for Molecular Medicine Cologne (CMMC), Cologne Center for Genomics (CCG), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; nuernberg@uni-koeln.de"],["dc.contributor.affiliation","Ott, Claus-Eric; 34Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, Germany; claus-eric.ott@charite.de"],["dc.contributor.affiliation","Peters, Annette; 19Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; christian.gieger@helmholtz-muenchen.de (C.G.); peters@helmholtz-muenchen.de (A.P.)"],["dc.contributor.affiliation","Pharoah, Paul D. P.; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Ramirez, Alfredo; 36Division for Neurogenetics and Molecular Psychiatry, Medical Faculty, University of Cologne, 50937 Cologne, Germany; alfredo.ramirez@uk-koeln.de"],["dc.contributor.affiliation","Ramser, Juliane; 37Division of Gynaecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität München, 81675 Munich, Germany; juliane.ramser@mri.tum.de (J.R.); alfons.meindl@gmx.de (A.M.)"],["dc.contributor.affiliation","Riedel-Heller, Steffi; 38Institute of Social Medicine, Occupational Health and Public Health, Faculty of Medicine, University of Leipzig, 04103 Leipzig, Germany; steffi.riedel-heller@medizin.uni-leipzig.de"],["dc.contributor.affiliation","Schmidt, Gunnar; 39Institute of Human Genetics, Hannover Medical School, 30625 Hannover, Germany; schmidt.gunnar@mh-hannover.de"],["dc.contributor.affiliation","Shah, Mitul; 15Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; amd24@medschl.cam.ac.uk (A.M.D.); craig@srl.cam.ac.uk (C.L.); ms483@medschl.cam.ac.uk (M.S.)"],["dc.contributor.affiliation","Scherer, Martin; 40Department of Primary Medical Care, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; m.scherer@uke.de"],["dc.contributor.affiliation","Stäbler, Antje; 41Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; antje.staebler@med.uni-tuebingen.de"],["dc.contributor.affiliation","Strom, Tim M.; 10Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany; riccardo.berutti@helmholtz-muenchen.de (R.B.); tim.strom@tum.de (T.M.S.)"],["dc.contributor.affiliation","Sutter, Christian; 42Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany; christian.sutter@med.uni-heidelberg.de"],["dc.contributor.affiliation","Thiele, Holger; 7Cologne Center for Genomics (CCG), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; janine.altmueller@mdc-berlin.de (J.A.); holger.thiele@uni-koeln.de (H.T.)"],["dc.contributor.affiliation","van Asperen, Christi J.; 43Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, The Netherlands; c.j.van_asperen@lumc.nl (C.J.v.A.); r.b.van_der_luijt@lumc.nl (R.B.v.d.L.)"],["dc.contributor.affiliation","van der Kolk, Lizet; 5Family Cancer Clinic, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; m.adank@nki.nl (M.A.A.); f.hogervorst@nki.nl (F.B.L.H.); l.vd.kolk@nki.nl (L.v.d.K.)"],["dc.contributor.affiliation","van der Luijt, Rob B.; 43Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, The Netherlands; c.j.van_asperen@lumc.nl (C.J.v.A.); r.b.van_der_luijt@lumc.nl (R.B.v.d.L.)"],["dc.contributor.affiliation","Volk, Alexander E.; 45Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; a.volk@uke.de"],["dc.contributor.affiliation","Wagner, Michael; 46Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, 53127 Bonn, Germany; michael.wagner@ukbonn.de"],["dc.contributor.affiliation","Waisfisz, Quinten; 47Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 Amsterdam, The Netherlands; q.waisfisz@vumc.nl"],["dc.contributor.affiliation","Wang, Qin; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Wang-Gohrke, Shan; 48Department of Gynaecology and Obstetrics, University of Ulm, 89081 Ulm, Germany; shan.wang-gohrke@uniklinik-ulm.de"],["dc.contributor.affiliation","Weber, Bernhard H. F.; 49Institute of Human Genetics, Regensburg University, 93053 Regensburg, Germany; bweb@klinik.uni-regensburg.de"],["dc.contributor.affiliation","Devilee, Peter; 51Department of Pathology, Department of Human Genetics, Leiden University Medical Center, 2333 Leiden, The Netherlands; p.devilee@lumc.nl"],["dc.contributor.affiliation","Tavtigian, Sean; 4Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; sean.tavtigian@hci.utah.edu"],["dc.contributor.affiliation","Bader, Gary D.; 11Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; bull@lunenfeld.ca (S.B.); jessica.green@sinaihealth.ca (J.G.); gary.bader@utoronto.ca (G.D.B.); andrulis@lunenfeld.ca (I.L.A.)"],["dc.contributor.affiliation","Meindl, Alfons; 37Division of Gynaecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität München, 81675 Munich, Germany; juliane.ramser@mri.tum.de (J.R.); alfons.meindl@gmx.de (A.M.)"],["dc.contributor.affiliation","Goldgar, David E.; 3Department of Dermatology, University of Utah, Salt Lake City, UT 84103, USA; bingjian.feng@hsc.utah.edu (B.-J.F.); david.goldgar@hsc.utah.edu (D.E.G.)"],["dc.contributor.affiliation","Andrulis, Irene L.; 11Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; bull@lunenfeld.ca (S.B.); jessica.green@sinaihealth.ca (J.G.); gary.bader@utoronto.ca (G.D.B.); andrulis@lunenfeld.ca (I.L.A.)"],["dc.contributor.affiliation","Schmutzler, Rita K.; 2Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; nana.weber-lassalle@uk-koeln.de (N.W.-L.); corinna.ernst@uk-koeln.de (C.E.); rita.schmutzler@uk-koeln.de (R.K.S.); eric.hahnen@uk-koeln.de (E.H.)"],["dc.contributor.affiliation","Easton, Douglas F.; 6Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; jma@ebi.ac.uk (J.A.); mkh39@medschl.cam.ac.uk (M.K.B.); sc2017@medschl.cam.ac.uk (S.C.); paul.pharoah@medschl.cam.ac.uk (P.D.P.P.); qw232@medschl.cam.ac.uk (Q.W.); dfe20@medschl.cam.ac.uk (D.F.E.)"],["dc.contributor.affiliation","Schmidt, Marjanka K.; 13Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, The Netherlands; s.cornelissen@nki.nl (S.C.); r.keeman@nki.nl (R.K.); mk.schmidt@nki.nl (M.K.S.)"],["dc.contributor.affiliation","Hahnen, Eric; 2Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; nana.weber-lassalle@uk-koeln.de (N.W.-L.); corinna.ernst@uk-koeln.de (C.E.); rita.schmutzler@uk-koeln.de (R.K.S.); eric.hahnen@uk-koeln.de (E.H.)"],["dc.contributor.affiliation","Simard, Jacques; 1Genomics Center, CHU de Québec-Université Laval Research Center, 2705 Laurier Boulevard, Quebec City, QC GIV 4G2, Canada; martine.dumont@crchudequebec.ulaval.ca (M.D.); charles.joly-beauparlant@crchudequebec.ulaval.ca (C.J.-B.); arnaud.droit@crchudequebec.ulaval.ca (A.D.); stephane.dubois@crchudequebec.ulaval.ca (S.D.); annie-c.c-deschesnes@crchudequebec.ulaval.ca (A.-C.C.-D.); penny.soucy@crchudequebec.ulaval.ca (P.S.); maxime.vallee@chu-lyon.fr (M.V.); frederic.fournier.4@ulaval.ca (F.F.); audrey@mims.ai (A.L.)"],["dc.contributor.author","Dumont, Martine"],["dc.contributor.author","Weber-Lassalle, Nana"],["dc.contributor.author","Joly-Beauparlant, Charles"],["dc.contributor.author","Ernst, Corinna"],["dc.contributor.author","Droit, Arnaud"],["dc.contributor.author","Feng, Bing-Jian"],["dc.contributor.author","Dubois, Stéphane"],["dc.contributor.author","Collin-Deschesnes, Annie-Claude"],["dc.contributor.author","Soucy, Penny"],["dc.contributor.author","Vallée, Maxime"],["dc.contributor.author","Fournier, Frédéric"],["dc.contributor.author","Lemaçon, Audrey"],["dc.contributor.author","Adank, Muriel A."],["dc.contributor.author","Allen, Jamie"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Arnold, Norbert"],["dc.contributor.author","Ausems, Margreet G. E. M."],["dc.contributor.author","Berutti, Riccardo"],["dc.contributor.author","Bolla, Manjeet K."],["dc.contributor.author","Bull, Shelley"],["dc.contributor.author","Carvalho, Sara"],["dc.contributor.author","Cornelissen, Sten"],["dc.contributor.author","Dufault, Michael R."],["dc.contributor.author","Dunning, Alison M."],["dc.contributor.author","Engel, Christoph"],["dc.contributor.author","Gehrig, Andrea"],["dc.contributor.author","Geurts-Giele, Willemina R. R."],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Green, Jessica"],["dc.contributor.author","Hackmann, Karl"],["dc.contributor.author","Helmy, Mohamed"],["dc.contributor.author","Hentschel, Julia"],["dc.contributor.author","Hogervorst, Frans B. L."],["dc.contributor.author","Hollestelle, Antoinette"],["dc.contributor.author","Hooning, Maartje J."],["dc.contributor.author","Horváth, Judit"],["dc.contributor.author","Ikram, M. Arfan"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Keeman, Renske"],["dc.contributor.author","Kuang, Da"],["dc.contributor.author","Luccarini, Craig"],["dc.contributor.author","Maier, Wolfgang"],["dc.contributor.author","Martens, John W. M."],["dc.contributor.author","Niederacher, Dieter"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Ott, Claus-Eric"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Pharoah, Paul D. P."],["dc.contributor.author","Ramirez, Alfredo"],["dc.contributor.author","Ramser, Juliane"],["dc.contributor.author","Riedel-Heller, Steffi"],["dc.contributor.author","Schmidt, Gunnar"],["dc.contributor.author","Shah, Mitul"],["dc.contributor.author","Scherer, Martin"],["dc.contributor.author","Stäbler, Antje"],["dc.contributor.author","Strom, Tim M."],["dc.contributor.author","Sutter, Christian"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","van Asperen, Christi J."],["dc.contributor.author","van der Kolk, Lizet"],["dc.contributor.author","van der Luijt, Rob B."],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Waisfisz, Quinten"],["dc.contributor.author","Wang, Qin"],["dc.contributor.author","Wang-Gohrke, Shan"],["dc.contributor.author","Weber, Bernhard H. F."],["dc.contributor.author","Devilee, Peter"],["dc.contributor.author","Tavtigian, Sean"],["dc.contributor.author","Bader, Gary D."],["dc.contributor.author","Meindl, Alfons"],["dc.contributor.author","Goldgar, David E."],["dc.contributor.author","Andrulis, Irene L."],["dc.contributor.author","Schmutzler, Rita K."],["dc.contributor.author","Easton, Douglas F."],["dc.contributor.author","Schmidt, Marjanka K."],["dc.contributor.author","Hahnen, Eric"],["dc.contributor.author","Simard, Jacques"],["dc.date.accessioned","2022-08-04T08:22:05Z"],["dc.date.available","2022-08-04T08:22:05Z"],["dc.date.issued","2022-07-11"],["dc.date.updated","2022-08-03T11:52:48Z"],["dc.description.abstract","Genetic variants explaining approximately 40% of familial breast cancer risk have been identified, thus leaving a significant fraction of the heritability of this disease still unexplained. The exact nature of this missing fraction is unknown; more extensive sequencing efforts could potentially identify new moderate-penetrance breast cancer risk alleles. The aim of this study was to perform a large-scale whole-exome sequencing study, followed by a targeted validation, in breast cancer patients and healthy women of European descent. We identified 20 novel genes with modest evidence of association (p-value < 0.05) for either overall or subtype-specific breast cancer; however, much larger studies are needed to confirm the exact role of these genes in susceptibility to breast cancer.\r\n \r\n \r\n Abstract\r\n Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes."],["dc.description.sponsorship","Genome Canada"],["dc.description.sponsorship","Canadian Institutes of Health Research"],["dc.description.sponsorship","Genome Quebec"],["dc.description.sponsorship","Quebec Breast Cancer Foundation"],["dc.description.sponsorship","Ministère de l’Économie, de la Science et de l’Innovation du Québec"],["dc.description.sponsorship","U.S. National Institutes of Health, National Center for Research Resources"],["dc.identifier.doi","10.3390/cancers14143363"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112620"],["dc.language.iso","en"],["dc.relation.eissn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.title","Uncovering the Contribution of Moderate-Penetrance Susceptibility Genes to Breast Cancer by Whole-Exome Sequencing and Targeted Enrichment Sequencing of Candidate Genes in Women of European Ancestry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","34971"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","34979"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Gehrig, Julia"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Jarry, Hubertus"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Stettner, Mark"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Thelen, Paul"],["dc.date.accessioned","2018-11-07T10:23:41Z"],["dc.date.available","2018-11-07T10:23:41Z"],["dc.date.issued","2017"],["dc.description.abstract","Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin. In the present study, we demonstrate that stimulating estrogen receptor beta activity with the specific agonist 8 beta-VE2 in VCaP cells in successive stages of ADT induced a time-and dose-dependent decrease in cell survival and an increase in apoptosis. Furthermore, 8 beta-VE2 treatment reduced the overexpression of the AR as well as ARVs in VCaP cells under maximum ADT. Our results indicate that decreased survival of the androgen-dependent CRPC cells employing apoptosis together with the regulative effect on AR expression could have beneficial effects over current AR-targeting therapies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.18632/oncotarget.16496"],["dc.identifier.isi","000402051700085"],["dc.identifier.pmid","28380417"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42509"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Prospects of estrogen receptor beta activation in the treatment of castration-resistant prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","55"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Breast Cancer Research"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Weber-Lassalle, Nana"],["dc.contributor.author","Borde, Julika"],["dc.contributor.author","Weber-Lassalle, Konstantin"],["dc.contributor.author","Horváth, Judit"],["dc.contributor.author","Niederacher, Dieter"],["dc.contributor.author","Arnold, Norbert"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Ernst, Corinna"],["dc.contributor.author","Paul, Victoria G."],["dc.contributor.author","Honisch, Ellen"],["dc.contributor.author","Klaschik, Kristina"],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Kubisch, Christian"],["dc.contributor.author","Rapp, Steffen"],["dc.contributor.author","Lichey, Nadine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Lepkes, Louisa"],["dc.contributor.author","Pohl-Rescigno, Esther"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Larsen, Mirjam"],["dc.contributor.author","Richters, Lisa"],["dc.contributor.author","Rhiem, Kerstin"],["dc.contributor.author","Wappenschmidt, Barbara"],["dc.contributor.author","Engel, Christoph"],["dc.contributor.author","Meindl, Alfons"],["dc.contributor.author","Schmutzler, Rita K."],["dc.contributor.author","Hahnen, Eric"],["dc.contributor.author","Hauke, Jan"],["dc.date.accessioned","2019-07-09T11:51:25Z"],["dc.date.available","2019-07-09T11:51:25Z"],["dc.date.issued","2019"],["dc.description.abstract","BACKGROUND: The role of the BARD1 gene in breast cancer (BC) and ovarian cancer (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the role of deleterious BARD1 germline variants in BC/OC predisposition in a sample of 4920 BRCA1/2-negative female BC/OC index patients of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A total of 4469 female index patients with BC, 451 index patients with OC, and 2767 geographically matched female control individuals were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the inclusion criteria of the GC-HBOC for germline testing and reported at least one relative with BC or OC. Additional control datasets (Exome Aggregation Consortium, ExAC; Fabulous Ladies Over Seventy, FLOSSIES) were included for the calculation of odds ratios (ORs). RESULTS: We identified LoF variants in 23 of 4469 BC index patients (0.51%) and in 36 of 37,265 control individuals (0.10%), resulting in an OR of 5.35 (95% confidence interval [CI] = 3.17-9.04; P < 0.00001). BARD1-mutated BC index patients showed a significantly younger mean age at first diagnosis (AAD; 42.3 years, range 24-60 years) compared with the overall study sample (48.6 years, range 17-92 years; P = 0.00347). In the subgroup of BC index patients with an AAD < 40 years, an OR of 12.04 (95% CI = 5.78-25.08; P < 0.00001) was observed. An OR of 7.43 (95% CI = 4.26-12.98; P < 0.00001) was observed when stratified for an AAD < 50 years. LoF variants in BARD1 were not significantly associated with BC in the subgroup of index patients with an AAD ≥ 50 years (OR = 2.29; 95% CI = 0.82-6.45; P = 0.11217). Overall, rare and predicted damaging BARD1 missense variants were significantly more prevalent in BC index patients compared with control individuals (OR = 2.15; 95% CI = 1.26-3.67; P = 0.00723). Neither LoF variants nor predicted damaging rare missense variants in BARD1 were identified in 451 familial index patients with OC. CONCLUSIONS: Due to the significant association of germline LoF variants in BARD1 with early-onset BC, we suggest that intensified BC surveillance programs should be offered to women carrying pathogenic BARD1 gene variants."],["dc.identifier.doi","10.1186/s13058-019-1137-9"],["dc.identifier.pmid","31036035"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59944"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0200343"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Blesinger, Hannah"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Schwoch, Sonja"],["dc.contributor.author","Prantl, Lukas"],["dc.contributor.author","Rößler, Jochen"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Becker, Jürgen"],["dc.date.accessioned","2019-07-09T11:45:49Z"],["dc.date.available","2019-07-09T11:45:49Z"],["dc.date.issued","2018"],["dc.description.abstract","Lymphatic malformations (LM) are characterized by the overgrowth of lymphatic vessels during pre- and postnatal development. Macrocystic, microcystic and combined forms of LM are known. The cysts are lined by lymphatic endothelial cells (LECs). Resection and sclerotherapy are the most common treatment methods. Recent studies performed on LM specimens in the United States of America have identified activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene in LM. However, whole tissue but not isolated cell types were studied. Here, we studied LM tissues resected at the University Hospitals Freiburg and Regensburg, Germany. We isolated LECs and fibroblasts separately, and sequenced the commonly affected exons 8, 10, and 21 of the PIK3CA gene. We confirm typical monoallelic mutations in 4 out of 6 LM-derived LEC lines, and describe two new mutations i.) in exon 10 (c.1636C>A; p.Gln546Lys), and ii.) a 3bp in-frame deletion of GAA (Glu109del). LM-derived fibroblasts did not possess such mutations, showing cell-type specificity of the gene defect. High activity of the PIK3CA-AKT- mTOR pathway was demonstrated by hyperphosphorylation of AKT-Ser473 in all LM-derived LECs (including the ones with newly identified mutations), as compared to normal LECs. Additionally, hyperphosphorylation of ERK was seen in all LM-derived LECs, except for the one with Glu109del. In vitro, the small molecule kinase inhibitors Buparlisib/BKM-120, Wortmannin, and Ly294002, (all inhibitors of PIK3CA), CAL-101 (inhibitor of PIK3CD), MK-2206 (AKT inhibitor), Sorafenib (multiple kinases inhibitor), and rapamycin (mTOR inhibitor) significantly blocked proliferation of LM-derived LECs in a concentration-dependent manner, but also blocked proliferation of normal LECs. However, MK-2206 appeared to be more specific for mutated LECs, except in case of Glu109 deletion. In sum, children that are, or will be, treated with kinase inhibitors must be monitored closely."],["dc.identifier.doi","10.1371/journal.pone.0200343"],["dc.identifier.pmid","29985963"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59313"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1557"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","1578"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Parsons, Michael T."],["dc.contributor.author","Tudini, Emma"],["dc.contributor.author","Li, Hongyan"],["dc.contributor.author","Hahnen, Eric"],["dc.contributor.author","Wappenschmidt, Barbara"],["dc.contributor.author","Feliubadaló, Lidia"],["dc.contributor.author","Aalfs, Cora M."],["dc.contributor.author","Agata, Simona"],["dc.contributor.author","Aittomäki, Kristiina"],["dc.contributor.author","Alducci, Elisa"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Engel, Christoph"],["dc.contributor.author","Spurdle, Amanda B."],["dc.date.accessioned","2019-12-02T14:12:29Z"],["dc.date.accessioned","2021-10-27T13:21:42Z"],["dc.date.available","2019-12-02T14:12:29Z"],["dc.date.available","2021-10-27T13:21:42Z"],["dc.date.issued","2019"],["dc.description.abstract","The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification."],["dc.identifier.doi","10.1002/humu.23818"],["dc.identifier.eissn","1098-1004"],["dc.identifier.issn","1059-7794"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16801"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92041"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","549"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","553"],["dc.bibliographiccitation.volume","59"],["dc.contributor.affiliation","Yigit, Gökhan; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Sheffer, Ruth; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Daana, Muhannad; \r\n3\r\nChild Development Institute, Clalit Health Services, Tel Aviv, Israel"],["dc.contributor.affiliation","Li, Yun; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Kaygusuz, Emrah; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Mor-Shakad, Hagar; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Altmüller, Janine; \r\n5\r\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Nürnberg, Peter; \r\n5\r\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Douiev, Liza; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Kaulfuss, Silke; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Burfeind, Peter; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Wollnik, Bernd; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Brockmann, Knut; \r\n7\r\nInterdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Sheffer, Ruth"],["dc.contributor.author","Daana, Muhannad"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Kaygusuz, Emrah"],["dc.contributor.author","Mor-Shakad, Hagar"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Douiev, Liza"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2021-07-05T14:57:45Z"],["dc.date.available","2021-07-05T14:57:45Z"],["dc.date.issued","2021"],["dc.date.updated","2022-05-21T14:18:33Z"],["dc.description.abstract","Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1 . Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33 ) in family 1 and c.850C>T; p.(Gln284 ) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1 . All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance."],["dc.description.abstract","Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1 . Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33 ) in family 1 and c.850C>T; p.(Gln284 ) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1 . All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance."],["dc.identifier","34172529"],["dc.identifier.doi","10.1136/jmedgenet-2021-107769"],["dc.identifier.pmid","34172529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87729"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/396"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/311"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-441"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.eissn","1468-6244"],["dc.relation.issn","0022-2593"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in biallelic state"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Versemann, Lennart; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Patil, Shilpa; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Steuber, Benjamin; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Zhang, Zhe; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Kopp, Waltraut; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Krawczyk, Hannah Elisa; 2Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, 37075 Göttingen, Germany; elisa.krawczyk@outlook.de (H.E.K.); silke.kaulfuss@med.uni-goettingen.de (S.K.); bernd.wollnik@med.uni-goettingen.de (B.W.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Kaulfuß, Silke; 2Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, 37075 Göttingen, Germany; elisa.krawczyk@outlook.de (H.E.K.); silke.kaulfuss@med.uni-goettingen.de (S.K.); bernd.wollnik@med.uni-goettingen.de (B.W.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Wollnik, Bernd; 2Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, 37075 Göttingen, Germany; elisa.krawczyk@outlook.de (H.E.K.); silke.kaulfuss@med.uni-goettingen.de (S.K.); bernd.wollnik@med.uni-goettingen.de (B.W.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Ströbel, Philipp; 2Clinical Research Unit 5002, KFO5002, University Medical Center Göttingen, 37075 Göttingen, Germany; elisa.krawczyk@outlook.de (H.E.K.); silke.kaulfuss@med.uni-goettingen.de (S.K.); bernd.wollnik@med.uni-goettingen.de (B.W.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Neesse, Albrecht; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Singh, Shiv K.; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Ellenrieder, Volker; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Hessmann, Elisabeth; 1Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; lennart.versemann@t-online.de (L.V.); shilpapatil528@gmail.com (S.P.); benjamin.steuber@med.uni-goettingen.de (B.S.); zhe.zhang@med.uni-goettingen.de (Z.Z.); wkopp@med.uni-goettingen.de (W.K.); albrecht.neesse@med.uni-goettingen.de (A.N.); shiv.singh@med.uni-goettingen.de (S.K.S.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.author","Versemann, Lennart"],["dc.contributor.author","Patil, Shilpa"],["dc.contributor.author","Steuber, Benjamin"],["dc.contributor.author","Zhang, Zhe"],["dc.contributor.author","Kopp, Waltraut"],["dc.contributor.author","Krawczyk, Hannah Elisa"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.date.accessioned","2022-08-04T08:34:43Z"],["dc.date.available","2022-08-04T08:34:43Z"],["dc.date.issued","2022-07-15"],["dc.date.updated","2022-08-03T11:58:42Z"],["dc.description.abstract","Epigenetic alterations contribute to the aggressiveness and therapy resistance of Pancreatic Ductal Adenocarcinoma (PDAC). However, epigenetic regulators, including Enhancer of Zeste Homolog 2 (EZH2), reveal a strong context-dependent activity. Our study aimed to examine the context-defining molecular prerequisites of oncogenic EZH2 activity in PDAC to assess the therapeutic efficacy of targeting EZH2. Our preclinical study using diverse PDAC models demonstrates that the TP53 status determines oncogenic EZH2 activity. Only in TP53-wildtype (wt) PDAC subtypes was EZH2 blockade associated with a favorable PDAC prognosis mainly through cell-death response. We revealed that EZH2 depletion increases p53wt stability by the de-repression of CDKN2A. Therefore, our study provides preclinical evidence that an intact CDKN2A-p53wt axis is indispensable for a beneficial outcome of EZH2 depletion and highlights the significance of molecular stratification to improve epigenetic targeting in PDAC. \r\n \r\n \r\n Abstract\r\n Pancreatic Ductal Adenocarcinoma (PDAC) represents a lethal malignancy with a consistently poor outcome. Besides mutations in PDAC driver genes, the aggressive tumor biology of the disease and its remarkable therapy resistance are predominantly installed by potentially reversible epigenetic dysregulation. However, epigenetic regulators act in a context-dependent manner with opposing implication on tumor progression, thus critically determining the therapeutic efficacy of epigenetic targeting. Herein, we aimed at exploring the molecular prerequisites and underlying mechanisms of oncogenic Enhancer of Zeste Homolog 2 (EZH2) activity in PDAC progression. Preclinical studies in EZH2 proficient and deficient transgenic and orthotopic in vivo PDAC models and transcriptome analysis identified the TP53 status as a pivotal context-defining molecular cue determining oncogenic EZH2 activity in PDAC. Importantly, the induction of pro-apoptotic gene signatures and processes as well as a favorable PDAC prognosis upon EZH2 depletion were restricted to p53 wildtype (wt) PDAC subtypes. Mechanistically, we illustrate that EZH2 blockade de-represses CDKN2A transcription for the subsequent posttranslational stabilization of p53wt expression and function. Together, our findings suggest an intact CDKN2A-p53wt axis as a prerequisite for the anti-tumorigenic consequences of EZH2 depletion and emphasize the significance of molecular stratification for the successful implementation of epigenetic targeting in PDAC."],["dc.description.sponsorship","Wilhelm-Sander Stiftung"],["dc.description.sponsorship","German Cancer Aid"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Ministry for Science and Culture in Lower Saxony/Volkswagenstiftung"],["dc.description.sponsorship","China Scholarship Council"],["dc.identifier.doi","10.3390/cancers14143451"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112631"],["dc.language.iso","en"],["dc.relation.eissn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.title","TP53-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11778"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","11791"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Keitel, Ulrike"],["dc.contributor.author","Scheel, Andreas"],["dc.contributor.author","Thomale, Jürgen"],["dc.contributor.author","Halpape, Rovena"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Scheel, Christina"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2022-03-01T11:44:20Z"],["dc.date.available","2022-03-01T11:44:20Z"],["dc.date.issued","2014"],["dc.description.abstract","The transition from an epithelial to a mesenchymal phenotype (EMT) confers increased invasiveness and clonogenic potential to tumor cells. We used a breast epithelium-derived cell culture model to evaluate the impact of EMT on the cellular sensitivity towards chemotherapeutics and apoptotic stimuli. Cells that had passed through an EMT acquired resistance towards chemotherapeutics and death ligands. Mechanistically, we found that the levels of the apoptosis inhibitor Bcl-xL were strongly enhanced in mesenchymal versus epithelial cells, whereas the pro-apoptotic proteins Bim and Puma were diminished. Clinical samples from breast cancer showed enhanced Bcl-xL staining in cells that had dispersed into the desmoplastic stroma, as compared to cells that were part of large tumor cell aggregates, suggesting increased Bcl-xL expression when cells invade the stroma. Bcl-xL was necessary for apoptotic resistance in mesenchymal cells, and its expression was sufficient to confer such resistance to epithelial cells. To antagonize Bcl-xL, BH3-mimetics were used. They successfully interfered with the proliferation and survival of mesenchymal cells, and also inhibited the growth of xenograft tumors raised from the mesenchymal subpopulation. We conclude that enhanced Bcl-xL levels confer resistance to cells upon EMT, and that Bcl-xL represents a promising target for therapy directed against invasive cancer cells."],["dc.format.extent","14"],["dc.identifier.doi","10.18632/oncotarget.2634"],["dc.identifier.fs","610572"],["dc.identifier.pii","2634"],["dc.identifier.pmid","25473892"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11133"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102995"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1949-2553"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.ddc","610"],["dc.title","Bcl-xL mediates therapeutic resistance of a mesenchymal breast cancer cell subpopulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]