TY - JOUR A1 - Dornelas, Maria A1 - Antão, Laura H. A1 - Moyes, Faye A1 - Bates, Amanda E. A1 - Magurran, Anne E. A1 - Adam, Dušan A1 - Akhmetzhanova, Asem A. A1 - Appeltans, Ward A1 - Arcos, José Manuel A1 - Arnold, Haley A1 - Ayyappan, Narayanan A1 - Badihi, Gal A1 - Baird, Andrew H. A1 - Barbosa, Miguel A1 - Barreto, Tiago Egydio A1 - Bässler, Claus A1 - Bellgrove, Alecia A1 - Belmaker, Jonathan A1 - Benedetti-Cecchi, Lisandro A1 - Bett, Brian J. A1 - Bjorkman, Anne D. A1 - Błażewicz, Magdalena A1 - Blowes, Shane A. A1 - Bloch, Christopher P. Bloch A1 - Bonebrake, Timothy C. A1 - Boyd, Susan A1 - Bradford, Matt A1 - Brooks, Andrew J. A1 - Brown, James H. A1 - Bruelheide, Helge A1 - Budy, Phaedra A1 - Carvalho, Fernando A1 - Castañeda-Moya, Edward A1 - Chen, Chaolun Allen A1 - Chamblee, John F. A1 - Chase, Tory J. A1 - Siegwart Collier, Laura A1 - Collinge, Sharon K. A1 - Condit, Richard A1 - Cooper, Elisabeth J. A1 - Cornelissen, J. Hans C. A1 - Cotano, Unai A1 - Crow, Shannan Kyle A1 - Damasceno, Gabriella A1 - Davies, Claire H. A1 - Davis, Robert A. A1 - Day, Frank P. A1 - Degraer, Steven A1 - Doherty, Tim S. A1 - Dunn, Timothy E. A1 - Durigan, Giselda A1 - Duffy, J. Emmett A1 - Edelist, Dor A1 - Edgar, Graham J. A1 - Elahi, Robin A1 - Elmendorf, Sarah C. A1 - Enemar, Anders A1 - Ernest, S. K. Morgan A1 - Escribano, Rubén A1 - Estiarte, Marc A1 - Evans, Brian S. A1 - Fan, Tung-Yung A1 - Turini Farah, Fabiano A1 - Loureiro Fernandes, Luiz A1 - Farneda, Fábio Z. A1 - Fidelis, Alessandra A1 - Fitt, Robert A1 - Fosaa, Anna Maria A1 - Franco, Geraldo Antonio Daher Correa A1 - Frank, Grace E. A1 - Fraser, William R. A1 - García, Hernando A1 - Cazzolla Gatti, Roberto A1 - Givan, Or A1 - Gorgone-Barbosa, Elizabeth A1 - Gould, William A. A1 - Gries, Corinna A1 - Grossman, Gary D. A1 - Gutierréz, Julio R. A1 - Hale, Stephen A1 - Harmon, Mark E. A1 - Harte, John A1 - Haskins, Gary A1 - Henshaw, Donald L. A1 - Hermanutz, Luise A1 - Hidalgo, Pamela A1 - Higuchi, Pedro A1 - Hoey, Andrew A1 - Van Hoey, Gert A1 - Hofgaard, Annika A1 - Holeck, Kristen A1 - Hollister, Robert D. A1 - Holmes, Richard A1 - Hoogenboom, Mia A1 - Hsieh, Chih-hao A1 - Hubbell, Stephen P. A1 - Huettmann, Falk A1 - Huffard, Christine L. A1 - Hurlbert, Allen H. A1 - Ivanauskas, Natália Macedo A1 - Janík, David A1 - Jandt, Ute A1 - Jażdżewska, Anna A1 - Johannessen, Tore A1 - Johnstone, Jill A1 - Jones, Julia A1 - Jones, Faith A. M. A1 - Kang, Jungwon A1 - Kartawijaya, Tasrif A1 - Keeley, Erin C. A1 - Kelt, Douglas A. A1 - Kinnear, Rebecca A1 - Klanderud, Kari A1 - Knutsen, Halvor A1 - Koenig, Christopher C. A1 - Kortz, Alessandra R. A1 - Král, Kamil A1 - Kuhnz, Linda A. A1 - Kuo, Chao-Yang A1 - Kushner, David J. A1 - Laguionie-Marchais, Claire A1 - Lancaster, Lesley T. A1 - Lee, Cheol Min A1 - Lefcheck, Jonathan S. A1 - Lévesque, Esther A1 - Lightfoot, David A1 - Lloret, Francisco A1 - Lloyd, John D. A1 - López-Baucells, Adrià A1 - Louzao, Maite A1 - Madin, Joshua S. A1 - Magnússon, Borgþór A1 - Malamud, Shahar A1 - Matthews, Iain A1 - McFarland, Kent P. A1 - McGill, Brian A1 - McKnight, Diane A1 - McLarney, William O. A1 - Meador, Jason A1 - Meserve, Peter L. A1 - Metcalfe, Daniel J. A1 - Meyer, Christoph F. J. A1 - Michelsen, Anders A1 - Milchakova, Nataliya A1 - Moens, Tom A1 - Moland, Even A1 - Moore, Jon A1 - Moreira, Carolina Mathias A1 - Müller, Jörg A1 - Murphy, Grace A1 - Myers-Smith, Isla H. A1 - Myster, Randall W. A1 - Naumov, Andrew A1 - Neat, Francis A1 - Nelson, James A. A1 - Nelson, Michael Paul A1 - Newton, Stephen F. A1 - Norden, Natalia A1 - Oliver, Jeffrey C. A1 - Olsen, Esben M. A1 - Onipchenko, Vladimir G. A1 - Pabis, Krzysztof A1 - Pabst, Robert J. A1 - Paquette, Alain A1 - Pardede, Sinta A1 - Paterson, David M. A1 - Pélissier, Raphaël A1 - Peñuelas, Josep A1 - Pérez-Matus, Alejandro A1 - Pizarro, Oscar A1 - Pomati, Francesco A1 - Post, Eric A1 - Prins, Herbert H. T. A1 - Priscu, John C. A1 - Provoost, Pieter A1 - Prudic, Kathleen L. A1 - Pulliainen, Erkki A1 - Ramesh, B. R. A1 - Ramos, Olivia Mendivil A1 - Rassweiler, Andrew A1 - Rebelo, Jose Eduardo A1 - Reed, Daniel C. A1 - Reich, Peter B. A1 - Remillard, Suzanne M. A1 - Richardson, Anthony J. A1 - Richardson, J. Paul A1 - van Rijn, Itai A1 - Rocha, Ricardo A1 - Rivera-Monroy, Victor H. A1 - Rixen, Christian A1 - Robinson, Kevin P. A1 - Rodrigues, Ricardo Ribeiro A1 - de Cerqueira Rossa-Feres, Denise A1 - Rudstam, Lars A1 - Ruhl, Henry A1 - Ruz, Catalina S. A1 - Sampaio, Erica M. A1 - Rybicki, Nancy A1 - Rypel, Andrew A1 - Sal, Sofia A1 - Salgado, Beatriz A1 - Santos, Flavio A. M. A1 - Savassi-Coutinho, Ana Paula A1 - Scanga, Sara A1 - Schmidt, Jochen A1 - Schooley, Robert A1 - Setiawan, Fakhrizal A1 - Shao, Kwang-Tsao A1 - Shaver, Gaius R. A1 - Sherman, Sally A1 - Sherry, Thomas W. A1 - Siciński, Jacek A1 - Sievers, Caya A1 - da Silva, Ana Carolina A1 - da Silva, Fernando Rodrigues A1 - Silveira, Fabio L. A1 - Slingsby, Jasper A1 - Smart, Tracey A1 - Snell, Sara J. A1 - Soudzilovskaia, Nadejda A. A1 - Souza, Gabriel B. G. A1 - Souza, Flaviana Maluf A1 - Souza, Vinícius Castro A1 - Stallings, Christopher D. A1 - Stanforth, Rowan A1 - Stanley, Emily H. A1 - Sterza, José Mauro A1 - Stevens, Maarten A1 - Stuart-Smith, Rick A1 - Suarez, Yzel Rondon A1 - Supp, Sarah A1 - Tamashiro, Jorge Yoshio A1 - Tarigan, Sukmaraharja A1 - Thiede, Gary P. A1 - Thorn, Simon A1 - Tolvanen, Anne A1 - Toniato, Maria Teresa Zugliani A1 - Totland, Ørjan A1 - Twilley, Robert R. A1 - Vaitkus, Gediminas A1 - Valdivia, Nelson A1 - Vallejo, Martha Isabel A1 - Valone, Thomas J. A1 - Van Colen, Carl A1 - Vanaverbeke, Jan A1 - Venturoli, Fabio A1 - Verheye, Hans M. A1 - Vianna, Marcelo A1 - Vieira, Rui P. A1 - Vrška, Tomáš A1 - Vu, Con Quang A1 - Vu, Lien Van A1 - Waide, Robert B. A1 - Waldock, Conor A1 - Watts, Dave A1 - Webb, Sara A1 - Wesołowski, Tomasz A1 - White, Ethan P. A1 - Widdicombe, Claire E. A1 - Wilgers, Dustin A1 - Williams, Richard A1 - Williams, Stefan B. A1 - Williamson, Mark A1 - Willig, Michael R. A1 - Willis, Trevor J. A1 - Wipf, Sonja A1 - Woods, Kerry D. A1 - Woehler, Eric J. A1 - Zawada, Kyle A1 - Zettler, Michael L. T1 - BioTIME: A database of biodiversity time series for the Anthropocene JF - Global Ecology and Biogeography N2 - Motivation The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2). Time period and grain BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. Software format .csv and .SQL. KW - biodiversity KW - global KW - spatial KW - species richness KW - temporal KW - turnover Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222846 VL - 27 ER - TY - JOUR A1 - Couch, Fergus J. A1 - Wang, Xianshu A1 - McGuffog, Lesley A1 - Lee, Andrew A1 - Olswold, Curtis A1 - Kuchenbaecker, Karoline B. A1 - Soucy, Penny A1 - Fredericksen, Zachary A1 - Barrowdale, Daniel A1 - Dennis, Joe A1 - Gaudet, Mia M. A1 - Dicks, Ed A1 - Kosel, Matthew A1 - Healey, Sue A1 - Sinilnikova, Olga M. A1 - Lee, Adam A1 - Bacot, Françios A1 - Vincent, Daniel A1 - Hogervorst, Frans B. L. A1 - Peock, Susan A1 - Stoppa-Lyonnet, Dominique A1 - Jakubowska, Anna A1 - Radice, Paolo A1 - Schmutzler, Rita Katharina A1 - Domchek, Susan M. A1 - Piedmonte, Marion A1 - Singer, Christian F. A1 - Friedman, Eitan A1 - Thomassen, Mads A1 - Hansen, Thomas V. O. A1 - Neuhausen, Susan L. A1 - Szabo, Csilla I. A1 - Blanco, Ingnacio A1 - Greene, Mark H. A1 - Karlan, Beth Y. A1 - Garber, Judy A1 - Phelan, Catherine M. A1 - Weitzel, Jeffrey N. A1 - Montagna, Marco A1 - Olah, Edith A1 - Andrulis, Irene L. A1 - Godwin, Andrew K. A1 - Yannoukakos, Drakoulis A1 - Goldgar, David E. A1 - Caldes, Trinidad A1 - Nevanlinna, Heli A1 - Osorio, Ana A1 - Terry, Mary Beth A1 - Daly, Mary B. A1 - van Rensburg, Elisabeth J. A1 - Hamann, Ute A1 - Ramus, Susan J. A1 - Toland, Amanda Ewart A1 - Caligo, Maria A. A1 - Olopade, Olufunmilayo I. A1 - Tung, Nadine A1 - Claes, Kathleen A1 - Beattie, Mary S. A1 - Southey, Melissa C. A1 - Imyanitov, Evgeny N. A1 - Tischkowitz, Marc A1 - Janavicius, Ramunas A1 - John, Esther M. A1 - Kwong, Ava A1 - Diez, Orland A1 - Kwong, Ava A1 - Balmaña, Judith A1 - Barkardottir, Rosa B. A1 - Arun, Banu K. A1 - Rennert, Gad A1 - Teo, Soo-Hwang A1 - Ganz, Patricia A. A1 - Campbell, Ian A1 - van der Hout, Annemarie H. A1 - van Deurzen, Carolien H. M. A1 - Seynaeve, Caroline A1 - Garcia, Encarna B. Gómez A1 - van Leeuwen, Flora E. A1 - Meijers-Heijboer, Hanne E. J. A1 - Gille, Johannes J. P. A1 - Ausems, Magreet G. E. M. A1 - Blok, Marinus J. A1 - Ligtenberg, Marjolinjin J. L. A1 - Rookus, Matti A. A1 - Devilee, Peter A1 - Verhoef, Senno A1 - van Os, Theo A. M. A1 - Wijnen, Juul T. A1 - Frost, Debra A1 - Ellis, Steve A1 - Fineberg, Elena A1 - Platte, Radke A1 - Evans, D. Gareth A1 - Izatt, Luise A1 - Eeles, Rosalind A. A1 - Adlard, Julian A1 - Eccles, Diana M. A1 - Cook, Jackie A1 - Brewer, Carole A1 - Douglas, Fiona A1 - Hodgson, Shirley A1 - Morrison, Patrick J. A1 - Side, Lucy E. A1 - Donaldson, Alan A1 - Houghton, Catherine A1 - Rogers, Mark T. A1 - Dorkins, Huw A1 - Eason, Jacqueline A1 - Gregory, Helen A1 - McCann, Emma A1 - Murray, Alex A1 - Calender, Alain A1 - Hardouin, Agnès A1 - Berthet, Pascaline A1 - Delnatte, Capucine A1 - Nogues, Catherine A1 - Lasset, Christine A1 - Houdayer, Claude A1 - Leroux,, Dominique A1 - Rouleau, Etienne A1 - Prieur, Fabienne A1 - Damiola, Francesca A1 - Sobol, Hagay A1 - Coupier, Isabelle A1 - Venat-Bouvet, Laurence A1 - Castera, Laurent A1 - Gauthier-Villars, Marion A1 - Léoné, Mélanie A1 - Pujol, Pascal A1 - Mazoyer, Sylvie A1 - Bignon, Yves-Jean A1 - Zlowocka-Perlowska, Elzbieta A1 - Gronwald, Jacek A1 - Lubinski,, Jan A1 - Durda, Katarzyna A1 - Jaworska, Katarzyna A1 - Huzarski, Tomasz A1 - Spurdle, Amanda B. A1 - Viel, Alessandra A1 - Peissel, Bernhard A1 - Bonanni, Bernardo A1 - Melloni, Guilia A1 - Ottini, Laura A1 - Papi, Laura A1 - Varesco, Liliana A1 - Tibiletti, Maria Grazia A1 - Peterlongo, Paolo A1 - Volorio, Sara A1 - Manoukian, Siranoush A1 - Pensotti, Valeria A1 - Arnold, Norbert A1 - Engel, Christoph A1 - Deissler, Helmut A1 - Gadzicki, Dorothea A1 - Gehrig, Andrea A1 - Kast, Karin A1 - Rhiem, Kerstin A1 - Meindl, Alfons A1 - Niederacher, Dieter A1 - Ditsch, Nina A1 - Plendl, Hansjoerg A1 - Preisler-Adams, Sabine A1 - Engert, Stefanie A1 - Sutter, Christian A1 - Varon-Mateeva, Raymenda A1 - Wappenschmidt, Barbara A1 - Weber, Bernhard H. F. A1 - Arver, Brita A1 - Stenmark-Askmalm, Marie A1 - Loman, Niklas A1 - Rosenquist, Richard A1 - Einbeigi, Zakaria A1 - Nathanson, Katherine L. A1 - Rebbeck, Timothy R. A1 - Blank, Stephanie V. A1 - Cohn, David E. A1 - Rodriguez, Gustavo C. A1 - Small, Laurie A1 - Friedlander, Michael A1 - Bae-Jump, Victoria L. A1 - Fink-Retter, Anneliese A1 - Rappaport, Christine A1 - Gschwantler-Kaulich, Daphne A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Lindor, Noralane M. A1 - Kaufman, Bella A1 - Paluch, Shani Shimon A1 - Laitman, Yael A1 - Skytte, Anne-Bine A1 - Gerdes, Anne-Marie A1 - Pedersen, Inge Sokilde A1 - Moeller, Sanne Traasdahl A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Vijai, Joseph A1 - Sarrel, Kara A1 - Robson, Mark A1 - Kauff, Noah A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Ozcelik, Hilmi A1 - Ejlertsen, Bent A1 - Nielsen, Finn C. A1 - Jønson, Lars A1 - Andersen, Mette K. A1 - Ding, Yuan Chun A1 - Steele, Linda A1 - Foretova, Lenka A1 - Teulé, Alex A1 - Lazaro, Conxi A1 - Brunet, Joan A1 - Pujana, Miquel Angel A1 - Mai, Phuong L. A1 - Loud, Jennifer T. A1 - Walsh, Christine A1 - Lester, Jenny A1 - Orsulic, Sandra A1 - Narod, Steven A. A1 - Herzog, Josef A1 - Sand, Sharon R. A1 - Tognazzo, Silvia A1 - Agata, Simona A1 - Vaszko, Tibor A1 - Weaver, Joellen A1 - Stravropoulou, Alexandra V. A1 - Buys, Saundra S. A1 - Romero, Atocha A1 - de la Hoya, Miguel A1 - Aittomäki, Kristiina A1 - Muranen, Taru A. A1 - Duran, Mercedes A1 - Chung, Wendy K. A1 - Lasa, Adriana A1 - Dorfling, Cecilia M. A1 - Miron, Alexander A1 - Benitez, Javier A1 - Senter, Leigha A1 - Huo, Dezheng A1 - Chan, Salina B. A1 - Sokolenko, Anna P. A1 - Chiquette, Jocelyne A1 - Tihomirova, Laima A1 - Friebel, Tara M. A1 - Agnarsson, Bjarne A. A1 - Lu, Karen H. A1 - Lejbkowicz, Flavio A1 - James, Paul A. A1 - Hall, Per A1 - Dunning, Alison M. A1 - Tessier, Daniel A1 - Cunningham, Julie A1 - Slager, Susan L. A1 - Chen, Wang A1 - Hart, Steven A1 - Stevens, Kristen A1 - Simard, Jacques A1 - Pastinen, Tomi A1 - Pankratz, Vernon S. A1 - Offit, Kenneth A1 - Easton, Douglas F. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. T1 - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk JF - PLOS Genetics N2 - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. KW - common variants KW - susceptibility alleles KW - genetic variants KW - modifiers KW - ZNF365 KW - investigators KW - population KW - consortium KW - selection KW - subtypes Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947 SN - 1553-7404 VL - 9 IS - 3 ER - TY - JOUR A1 - Blanco, Ignacio A1 - Kuchenbaecker, Karoline A1 - Cuadras, Daniel A1 - Wang, Xianshu A1 - Barrowdale, Daniel A1 - Ruiz de Garibay, Gorka A1 - Librado, Pablo A1 - Sanchez-Gracia, Alejandro A1 - Rozas, Julio A1 - Bonifaci, Núria A1 - McGuffog, Lesley A1 - Pankratz, Vernon S. A1 - Islam, Abul A1 - Mateo, Francesca A1 - Berenguer, Antoni A1 - Petit, Anna A1 - Català, Isabel A1 - Brunet, Joan A1 - Feliubadaló, Lidia A1 - Tornero, Eva A1 - Benítez, Javier A1 - Osorio, Ana A1 - Ramón y Cajal, Teresa A1 - Nevanlinna, Heli A1 - Aittomäki, Kristina A1 - Arun, Banu K. A1 - Toland, Amanda E. A1 - Karlan, Beth Y. A1 - Walsh, Christine A1 - Lester, Jenny A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Nussbaum, Robert L. A1 - Andrulis, Irene L. A1 - Domchek, Susan M. A1 - Nathanson, Katherine L. A1 - Rebbeck, Timothy R. A1 - Barkardottir, Rosa B. A1 - Jakubowska, Anna A1 - Lubinski, Jan A1 - Durda, Katarzyna A1 - Jaworska-Bieniek, Katarzyna A1 - Claes, Kathleen A1 - Van Maerken, Tom A1 - Díez, Orland A1 - Hansen, Thomas V. A1 - Jønson, Lars A1 - Gerdes, Anne-Marie A1 - Ejlertsen, Bent A1 - De la Hoya, Miguel A1 - Caldés, Trinidad A1 - Dunning, Alison M. A1 - Oliver, Clare A1 - Fineberg, Elena A1 - Cook, Margaret A1 - Peock, Susan A1 - McCann, Emma A1 - Murray, Alex A1 - Jacobs, Chris A1 - Pichert, Gabriella A1 - Lalloo, Fiona A1 - Chu, Carol A1 - Dorkins, Huw A1 - Paterson, Joan A1 - Ong, Kai-Ren A1 - Teixeira, Manuel R. A1 - Hogervorst, Frans B. L. A1 - Van der Hout, Annemarie H. A1 - Seynaeve, Caroline A1 - Van der Luijt, Rob B. A1 - Ligtenberg, Marjolijn J. L. A1 - Devilee, Peter A1 - Wijnen, Juul T. A1 - Rookus, Matti A. A1 - Meijers-Heijboer, Hanne E. J. A1 - Blok, Marinus J. A1 - Van den Ouweland, Ans M. W. A1 - Aalfs, Cora M. A1 - Rodriguez, Gustavo C. A1 - Phillips, Kelly-Anne A. A1 - Piedmonte, Marion A1 - Nerenstone, Stacy R. A1 - Bae-Jump, Victoria L. A1 - O'Malley, David M. A1 - Schmutzler, Rita K. A1 - Wappenschmidt, Barbara A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Meindl, Alfons A1 - Ditsch, Nina A1 - Arnold, Norbert A1 - Plendl, Hansjoerg J. A1 - Niederacher, Dieter A1 - Sutter, Christian A1 - Wang-Gohrke, Shan A1 - Steinemann, Doris A1 - Preisler-Adams, Sabine A1 - Kast, Karin A1 - Varon-Mateeva, Raymonda A1 - Gehrig, Andrea A1 - Bojesen, Anders A1 - Pedersen, Inge Sokilde A1 - Sunde, Lone A1 - Birk Jensen, Uffe A1 - Thomassen, Mads A1 - Kruse, Torben A. A1 - Foretova, Lenka A1 - Peterlongo, Paolo A1 - Bernard, Loris A1 - Peissel, Bernard A1 - Scuvera, Giulietta A1 - Manoukian, Siranoush A1 - Radice, Paolo A1 - Ottini, Laura A1 - Montagna, Marco A1 - Agata, Simona A1 - Maugard, Christine A1 - Simard, Jacques A1 - Soucy, Penny A1 - Berger, Andreas A1 - Fink-Retter, Anneliese A1 - Singer, Christian F. A1 - Rappaport, Christine A1 - Geschwantler-Kaulich, Daphne A1 - Tea, Muy-Kheng A1 - Pfeiler, Georg A1 - John, Esther M. A1 - Miron, Alex A1 - Neuhausen, Susan L. A1 - Terry, Mary Beth A1 - Chung, Wendy K. A1 - Daly, Mary B. A1 - Goldgar, David E. A1 - Janavicius, Ramunas A1 - Dorfling, Cecilia M. A1 - Van Rensburg, Elisabeth J. A1 - Fostira, Florentia A1 - Konstantopoulou, Irene A1 - Garber, Judy A1 - Godwin, Andrew K. A1 - Olah, Edith A1 - Narod, Steven A. A1 - Rennert, Gad A1 - Paluch, Shani Shimon A1 - Laitman, Yael A1 - Friedman, Eitan A1 - Liljegren, Annelie A1 - Rantala, Johanna A1 - Stenmark-Askmalm, Marie A1 - Loman, Niklas A1 - Imyanitov, Evgeny N. A1 - Hamann, Ute A1 - Spurdle, Amanda B. A1 - Healey, Sue A1 - Weitzel, Jeffrey N. A1 - Herzog, Josef A1 - Margileth, David A1 - Gorrini, Chiara A1 - Esteller, Manel A1 - Gómez, Antonio A1 - Sayols, Sergi A1 - Vidal, Enrique A1 - Heyn, Holger A1 - Stoppa-Lyonnet, Dominique A1 - Léoné, Melanie A1 - Barjhoux, Laure A1 - Fassy-Colcombet, Marion A1 - Pauw, Antoine de A1 - Lasset, Christine A1 - Fert Ferrer, Sandra A1 - Castera, Laurent A1 - Berthet, Pascaline A1 - Cornelis, François A1 - Bignon, Yves-Jean A1 - Damiola, Francesca A1 - Mazoyer, Sylvie A1 - Sinilnikova, Olga M. A1 - Maxwell, Christopher A. A1 - Vijai, Joseph A1 - Robson, Mark A1 - Kauff, Noah A1 - Corines, Marina J. A1 - Villano, Danylko A1 - Cunningham, Julie A1 - Lee, Adam A1 - Lindor, Noralane A1 - Lázaro, Conxi A1 - Easton, Douglas F. A1 - Offit, Kenneth A1 - Chenevix-Trench, Georgia A1 - Couch, Fergus J. A1 - Antoniou, Antonis C. A1 - Pujana, Miguel Angel T1 - Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers JF - PLoS ONE N2 - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. KW - genetic interaction networks KW - genome-wide association KW - expression signature KW - susceptibility loci KW - survival KW - modifiers KW - polymorphism KW - cell KW - chip-seq KW - elements Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143469 VL - 10 IS - 4 ER - TY - JOUR A1 - Hudson, Lawrence N. A1 - Newbold, Tim A1 - Contu, Sara A1 - Hill, Samantha L. L. A1 - Lysenko, Igor A1 - De Palma, Adriana A1 - Phillips, Helen R. P. A1 - Senior, Rebecca A. A1 - Bennett, Dominic J. A1 - Booth, Hollie A1 - Choimes, Argyrios A1 - Correia, David L. P. A1 - Day, Julie A1 - Echeverria-Londono, Susy A1 - Garon, Morgan A1 - Harrison, Michelle L. K. A1 - Ingram, Daniel J. A1 - Jung, Martin A1 - Kemp, Victoria A1 - Kirkpatrick, Lucinda A1 - Martin, Callum D. A1 - Pan, Yuan A1 - White, Hannah J. A1 - Aben, Job A1 - Abrahamczyk, Stefan A1 - Adum, Gilbert B. A1 - Aguilar-Barquero, Virginia A1 - Aizen, Marcelo A1 - Ancrenaz, Marc A1 - Arbelaez-Cortes, Enrique A1 - Armbrecht, Inge A1 - Azhar, Badrul A1 - Azpiroz, Adrian B. A1 - Baeten, Lander A1 - Báldi, András A1 - Banks, John E. A1 - Barlow, Jos A1 - Batáry, Péter A1 - Bates, Adam J. A1 - Bayne, Erin M. A1 - Beja, Pedro A1 - Berg, Ake A1 - Berry, Nicholas J. A1 - Bicknell, Jake E. A1 - Bihn, Jochen H. A1 - Böhning-Gaese, Katrin A1 - Boekhout, Teun A1 - Boutin, Celine A1 - Bouyer, Jeremy A1 - Brearley, Francis Q. A1 - Brito, Isabel A1 - Brunet, Jörg A1 - Buczkowski, Grzegorz A1 - Buscardo, Erika A1 - Cabra-Garcia, Jimmy A1 - Calvino-Cancela, Maria A1 - Cameron, Sydney A. A1 - Cancello, Eliana M. A1 - Carrijo, Tiago F. A1 - Carvalho, Anelena L. A1 - Castro, Helena A1 - Castro-Luna, Alejandro A. A1 - Cerda, Rolando A1 - Cerezo, Alexis A1 - Chauvat, Matthieu A1 - Clarke, Frank M. A1 - Cleary, Daniel F. R. A1 - Connop, Stuart P. A1 - D'Aniello, Biagio A1 - da Silva, Pedro Giovani A1 - Darvill, Ben A1 - Dauber, Jens A1 - Dejean, Alain A1 - Diekötter, Tim A1 - Dominguez-Haydar, Yamileth A1 - Dormann, Carsten F. A1 - Dumont, Bertrand A1 - Dures, Simon G. A1 - Dynesius, Mats A1 - Edenius, Lars A1 - Elek, Zoltán A1 - Entling, Martin H. A1 - Farwig, Nina A1 - Fayle, Tom M. A1 - Felicioli, Antonio A1 - Felton, Annika M. A1 - Ficetola, Gentile F. A1 - Filgueiras, Bruno K. C. A1 - Fonte, Steve J. A1 - Fraser, Lauchlan H. A1 - Fukuda, Daisuke A1 - Furlani, Dario A1 - Ganzhorn, Jörg U. A1 - Garden, Jenni G. A1 - Gheler-Costa, Carla A1 - Giordani, Paolo A1 - Giordano, Simonetta A1 - Gottschalk, Marco S. A1 - Goulson, Dave A1 - Gove, Aaron D. A1 - Grogan, James A1 - Hanley, Mick E. A1 - Hanson, Thor A1 - Hashim, Nor R. A1 - Hawes, Joseph E. A1 - Hébert, Christian A1 - Helden, Alvin J. A1 - Henden, John-André A1 - Hernández, Lionel A1 - Herzog, Felix A1 - Higuera-Diaz, Diego A1 - Hilje, Branko A1 - Horgan, Finbarr G. A1 - Horváth, Roland A1 - Hylander, Kristoffer A1 - Horváth, Roland A1 - Isaacs-Cubides, Paola A1 - Ishitani, Mashiro A1 - Jacobs, Carmen T. A1 - Jaramillo, Victor J. A1 - Jauker, Birgit A1 - Jonsell, Matts A1 - Jung, Thomas S. A1 - Kapoor, Vena A1 - Kati, Vassiliki A1 - Katovai, Eric A1 - Kessler, Michael A1 - Knop, Eva A1 - Kolb, Annette A1 - Körösi, Àdám A1 - Lachat, Thibault A1 - Lantschner, Victoria A1 - Le Féon, Violette A1 - LeBuhn, Gretchen A1 - Légaré, Jean-Philippe A1 - Letcher, Susan G. A1 - Littlewood, Nick A. A1 - López-Quintero, Carlos A. A1 - Louhaichi, Mounir A1 - Lövei, Gabor L. A1 - Lucas-Borja, Manuel Esteban A1 - Luja, Victor H. A1 - Maeto, Kaoru A1 - Magura, Tibor A1 - Mallari, Neil Aldrin A1 - Marin-Spiotta, Erika A1 - Marhall, E. J. P. A1 - Martínez, Eliana A1 - Mayfield, Margaret M. A1 - Mikusinski, Gregorz A1 - Milder, Jeffery C. A1 - Miller, James R. A1 - Morales, Carolina L. A1 - Muchane, Mary N. A1 - Muchane, Muchai A1 - Naidoo, Robin A1 - Nakamura, Akihiro A1 - Naoe, Shoji A1 - Nates-Parra, Guiomar A1 - Navarerete Gutierrez, Dario A. A1 - Neuschulz, Eike L. A1 - Noreika, Norbertas A1 - Norfolk, Olivia A1 - Noriega, Jorge Ari A1 - Nöske, Nicole M. A1 - O'Dea, Niall A1 - Oduro, William A1 - Ofori-Boateng, Caleb A1 - Oke, Chris O. A1 - Osgathorpe, Lynne M. A1 - Paritsis, Juan A1 - Parrah, Alejandro A1 - Pelegrin, Nicolás A1 - Peres, Carlos A. A1 - Persson, Anna S. A1 - Petanidou, Theodora A1 - Phalan, Ben A1 - Philips, T. Keith A1 - Poveda, Katja A1 - Power, Eileen F. A1 - Presley, Steven J. A1 - Proença, Vânia A1 - Quaranta, Marino A1 - Quintero, Carolina A1 - Redpath-Downing, Nicola A. A1 - Reid, J. Leighton A1 - Reis, Yana T. A1 - Ribeiro, Danilo B. A1 - Richardson, Barbara A. A1 - Richardson, Michael J. A1 - Robles, Carolina A. A1 - Römbke, Jörg A1 - Romero-Duque, Luz Piedad A1 - Rosselli, Loreta A1 - Rossiter, Stephen J. A1 - Roulston, T'ai H. A1 - Rousseau, Laurent A1 - Sadler, Jonathan P. A1 - Sáfián, Szbolcs A1 - Saldaña-Vásquez, Romeo A. A1 - Samnegård, Ulrika A1 - Schüepp, Christof A1 - Schweiger, Oliver A1 - Sedlock, Jodi L. A1 - Shahabuddin, Ghazala A1 - Sheil, Douglas A1 - Silva, Fernando A. B. A1 - Slade, Eleanor A1 - Smith-Pardo, Allan H. A1 - Sodhi, Navjot S. A1 - Somarriba, Eduardo J. A1 - Sosa, Ramón A. A1 - Stout, Jane C. A1 - Struebig, Matthew J. A1 - Sung, Yik-Hei A1 - Threlfall, Caragh G. A1 - Tonietto, Rebecca A1 - Tóthmérész, Béla A1 - Tscharntke, Teja A1 - Turner, Edgar C. A1 - Tylianakis, Jason M. A1 - Vanbergen, Adam J. A1 - Vassilev, Kiril A1 - Verboven, Hans A. F. A1 - Vergara, Carlos H. A1 - Vergara, Pablo M. A1 - Verhulst, Jort A1 - Walker, Tony R. A1 - Wang, Yanping A1 - Watling, James I. A1 - Wells, Konstans A1 - Williams, Christopher D. A1 - Willig, Michael R. A1 - Woinarski, John C. Z. A1 - Wolf, Jan H. D. A1 - Woodcock, Ben A. A1 - Yu, Douglas W. A1 - Zailsev, Andreys A1 - Collen, Ben A1 - Ewers, Rob M. A1 - Mace, Georgina M. A1 - Purves, Drew W. A1 - Scharlemann, Jörn P. W. A1 - Pervis, Andy T1 - The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts JF - Ecology and Evolution N2 - Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015. KW - urban-rural gradient KW - instensively managed farmland KW - Mexican coffee plantations KW - Bombus Spp. Hymenoptera KW - bumblebee nest density KW - data sharing KW - land use KW - habitat destruction KW - global change KW - land-use change KW - plant community composition KW - Northeastern Costa Rica KW - dung beetle coleoptera KW - bird species richness Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114425 VL - 4 IS - 24 ER - TY - JOUR A1 - Viljur, Mari‐Liis A1 - Abella, Scott R. A1 - Adámek, Martin A1 - Alencar, Janderson Batista Rodrigues A1 - Barber, Nicholas A. A1 - Beudert, Burkhard A1 - Burkle, Laura A. A1 - Cagnolo, Luciano A1 - Campos, Brent R. A1 - Chao, Anne A1 - Chergui, Brahim A1 - Choi, Chang‐Yong A1 - Cleary, Daniel F. R. A1 - Davis, Thomas Seth A1 - Dechnik‐Vázquez, Yanus A. A1 - Downing, William M. A1 - Fuentes‐Ramirez, Andrés A1 - Gandhi, Kamal J. K. A1 - Gehring, Catherine A1 - Georgiev, Kostadin B. A1 - Gimbutas, Mark A1 - Gongalsky, Konstantin B. A1 - Gorbunova, Anastasiya Y. A1 - Greenberg, Cathryn H. A1 - Hylander, Kristoffer A1 - Jules, Erik S. A1 - Korobushkin, Daniil I. A1 - Köster, Kajar A1 - Kurth, Valerie A1 - Lanham, Joseph Drew A1 - Lazarina, Maria A1 - Leverkus, Alexandro B. A1 - Lindenmayer, David A1 - Marra, Daniel Magnabosco A1 - Martín‐Pinto, Pablo A1 - Meave, Jorge A. A1 - Moretti, Marco A1 - Nam, Hyun‐Young A1 - Obrist, Martin K. A1 - Petanidou, Theodora A1 - Pons, Pere A1 - Potts, Simon G. A1 - Rapoport, Irina B. A1 - Rhoades, Paul R. A1 - Richter, Clark A1 - Saifutdinov, Ruslan A. A1 - Sanders, Nathan J. A1 - Santos, Xavier A1 - Steel, Zachary A1 - Tavella, Julia A1 - Wendenburg, Clara A1 - Wermelinger, Beat A1 - Zaitsev, Andrey S. A1 - Thorn, Simon T1 - The effect of natural disturbances on forest biodiversity: an ecological synthesis JF - Biological Reviews N2 - Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human‐induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land‐use change. Conversely, the suppression of natural disturbances threatens disturbance‐dependent biota. Using a meta‐analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α‐diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground‐dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α‐diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta‐analysis by applying a unified diversity concept based on Hill numbers to estimate α‐diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity–disturbance relationships are shaped by species relative abundances. Our synthesis of α‐diversity was extended by a synthesis of disturbance‐induced change in species assemblages, and revealed that disturbance changes the β‐diversity of multiple taxonomic groups, including some groups that were not affected at the α‐diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α‐diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes. KW - natural disturbance KW - diversity–disturbance relationship KW - disturbance severity KW - disturbance extent KW - intermediate disturbance hypothesis KW - forest communities KW - α‐diversity KW - β‐diversity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287168 VL - 97 IS - 5 SP - 1930 EP - 1947 ER - TY - JOUR A1 - Pinkawa, Michael A1 - Aebersold, Daniel M. A1 - Böhmer, Dirk A1 - Flentje, Michael A1 - Ghadjar, Pirus A1 - Schmidt-Hegemann, Nina-Sophie A1 - Höcht, Stefan A1 - Hölscher, Tobias A1 - Müller, Arndt-Christian A1 - Niehoff, Peter A1 - Sedlmayer, Felix A1 - Wolf, Frank A1 - Zamboglou, Constantinos A1 - Zips, Daniel A1 - Wiegel, Thomas T1 - Radiotherapy in nodal oligorecurrent prostate cancer JF - Strahlentherapie und Onkologie N2 - Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations. KW - prostate cancer KW - oligorecurrence KW - metastasis-directed therapy KW - radiation therapy KW - androgen deprivation therapy KW - stereotactic body radiotherapy KW - oligmometastases KW - lymph node metastases Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307763 SN - 0179-7158 SN - 1439-099X VL - 197 IS - 7 ER - TY - JOUR A1 - Gröbner, Susanne N. A1 - Worst, Barbara C. A1 - Weischenfeldt, Joachim A1 - Buchhalter, Ivo A1 - Kleinheinz, Kortine A1 - Rudneva, Vasilisa A. A1 - Johann, Pascal D. A1 - Balasubramanian, Gnana Prakash A1 - Segura-Wang, Maia A1 - Brabetz, Sebastian A1 - Bender, Sebastian A1 - Hutter, Barbara A1 - Sturm, Dominik A1 - Pfaff, Elke A1 - Hübschmann, Daniel A1 - Zipprich, Gideon A1 - Heinold, Michael A1 - Eils, Jürgen A1 - Lawerenz, Christian A1 - Erkek, Serap A1 - Lambo, Sander A1 - Waszak, Sebastian A1 - Blattmann, Claudia A1 - Borkhardt, Arndt A1 - Kuhlen, Michaela A1 - Eggert, Angelika A1 - Fulda, Simone A1 - Gessler, Manfred A1 - Wegert, Jenny A1 - Kappler, Roland A1 - Baumhoer, Daniel A1 - Stefan, Burdach A1 - Kirschner-Schwabe, Renate A1 - Kontny, Udo A1 - Kulozik, Andreas E. A1 - Lohmann, Dietmar A1 - Hettmer, Simone A1 - Eckert, Cornelia A1 - Bielack, Stefan A1 - Nathrath, Michaela A1 - Niemeyer, Charlotte A1 - Richter, Günther H. A1 - Schulte, Johannes A1 - Siebert, Reiner A1 - Westermann, Frank A1 - Molenaar, Jan J. A1 - Vassal, Gilles A1 - Witt, Hendrik A1 - Burkhardt, Birgit A1 - Kratz, Christian P. A1 - Witt, Olaf A1 - van Tilburg, Cornelis M. A1 - Kramm, Christof M. A1 - Fleischhack, Gudrun A1 - Dirksen, Uta A1 - Rutkowski, Stefan A1 - Frühwald, Michael A1 - Hoff, Katja von A1 - Wolf, Stephan A1 - Klingebeil, Thomas A1 - Koscielniak, Ewa A1 - Landgraf, Pablo A1 - Koster, Jan A1 - Resnick, Adam C. A1 - Zhang, Jinghui A1 - Liu, Yanling A1 - Zhou, Xin A1 - Waanders, Angela J. A1 - Zwijnenburg, Danny A. A1 - Raman, Pichai A1 - Brors, Benedikt A1 - Weber, Ursula D. A1 - Northcott, Paul A. A1 - Pajtler, Kristian W. A1 - Kool, Marcel A1 - Piro, Rosario M. A1 - Korbel, Jan O. A1 - Schlesner, Matthias A1 - Eils, Roland A1 - Jones, David T. W. A1 - Lichter, Peter A1 - Chavez, Lukas A1 - Zapatka, Marc A1 - Pfister, Stefan M. T1 - The landscape of genomic alterations across childhood cancers JF - Nature N2 - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials. KW - cancer genomics KW - oncogenesis KW - paediatric cancer KW - predictive markers KW - translational research Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579 VL - 555 ER - TY - JOUR A1 - Waszak, Sebastian M A1 - Northcott, Paul A A1 - Buchhalter, Ivo A1 - Robinson, Giles W A1 - Sutter, Christian A1 - Groebner, Susanne A1 - Grund, Kerstin B A1 - Brugières, Laurence A1 - Jones, David T W A1 - Pajtler, Kristian W A1 - Morrissy, A Sorana A1 - Kool, Marcel A1 - Sturm, Dominik A1 - Chavez, Lukas A1 - Ernst, Aurelie A1 - Brabetz, Sebastian A1 - Hain, Michael A1 - Zichner, Thomas A1 - Segura-Wang, Maia A1 - Weischenfeldt, Joachim A1 - Rausch, Tobias A1 - Mardin, Balca R A1 - Zhou, Xin A1 - Baciu, Cristina A1 - Lawerenz, Christian A1 - Chan, Jennifer A A1 - Varlet, Pascale A1 - Guerrini-Rousseau, Lea A1 - Fults, Daniel W A1 - Grajkowska, Wiesława A1 - Hauser, Peter A1 - Jabado, Nada A1 - Ra, Young-Shin A1 - Zitterbart, Karel A1 - Shringarpure, Suyash S A1 - De La Vega, Francisco M A1 - Bustamante, Carlos D A1 - Ng, Ho-Keung A1 - Perry, Arie A1 - MacDonald, Tobey J A1 - Driever, Pablo Hernáiz A1 - Bendel, Anne E A1 - Bowers, Daniel C A1 - McCowage, Geoffrey A1 - Chintagumpala, Murali M A1 - Cohn, Richard A1 - Hassall, Timothy A1 - Fleischhack, Gudrun A1 - Eggen, Tone A1 - Wesenberg, Finn A1 - Feychting, Maria A1 - Lannering, Birgitta A1 - Schüz, Joachim A1 - Johansen, Christoffer A1 - Andersen, Tina V A1 - Röösli, Martin A1 - Kuehni, Claudia E A1 - Grotzer, Michael A1 - Kjaerheim, Kristina A1 - Monoranu, Camelia M A1 - Archer, Tenley C A1 - Duke, Elizabeth A1 - Pomeroy, Scott L A1 - Shelagh, Redmond A1 - Frank, Stephan A1 - Sumerauer, David A1 - Scheurlen, Wolfram A1 - Ryzhova, Marina V A1 - Milde, Till A1 - Kratz, Christian P A1 - Samuel, David A1 - Zhang, Jinghui A1 - Solomon, David A A1 - Marra, Marco A1 - Eils, Roland A1 - Bartram, Claus R A1 - von Hoff, Katja A1 - Rutkowksi, Stefan A1 - Ramaswamy, Vijay A1 - Gilbertson, Richard J A1 - Korshunov, Andrey A1 - Taylor, Michael D A1 - Lichter, Peter A1 - Malkin, David A1 - Gajjar, Amar A1 - Korbel, Jan O A1 - Pfister, Stefan M T1 - Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort JF - The Lancet Oncology N2 - Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233425 VL - 19 ER - TY - JOUR A1 - Zaho, Huaying A1 - Ghirlando, Rodolfo A1 - Alfonso, Carlos A1 - Arisaka, Fumio A1 - Attali, Ilan A1 - Bain, David L. A1 - Bakhtina, Marina M. A1 - Becker, Donald F. A1 - Bedwell, Gregory J. A1 - Bekdemir, Ahmet A1 - Besong, Tabot M. D. A1 - Birck, Catherine A1 - Brautigam, Chad A. A1 - Brennerman, William A1 - Byron, Olwyn A1 - Bzowska, Agnieszka A1 - Chaires, Jonathan B. A1 - Chaton, Catherine T. A1 - Coelfen, Helmbut A1 - Connaghan, Keith D. A1 - Crowley, Kimberly A. A1 - Curth, Ute A1 - Daviter, Tina A1 - Dean, William L. A1 - Diez, Ana I. A1 - Ebel, Christine A1 - Eckert, Debra M. A1 - Eisele, Leslie E. A1 - Eisenstein, Edward A1 - England, Patrick A1 - Escalante, Carlos A1 - Fagan, Jeffrey A. A1 - Fairman, Robert A1 - Finn, Ron M. A1 - Fischle, Wolfgang A1 - Garcia de la Torre, Jose A1 - Gor, Jayesh A1 - Gustafsson, Henning A1 - Hall, Damien A1 - Harding, Stephen E. A1 - Hernandez Cifre, Jose G. A1 - Herr, Andrew B. A1 - Howell, Elizabeth E. A1 - Isaac, Richard S. A1 - Jao, Shu-Chuan A1 - Jose, Davis A1 - Kim, Soon-Jong A1 - Kokona, Bashkim A1 - Kornblatt, Jack A. A1 - Kosek, Dalibor A1 - Krayukhina, Elena A1 - Krzizike, Daniel A1 - Kusznir, Eric A. A1 - Kwon, Hyewon A1 - Larson, Adam A1 - Laue, Thomas M. A1 - Le Roy, Aline A1 - Leech, Andrew P. A1 - Lilie, Hauke A1 - Luger, Karolin A1 - Luque-Ortega, Juan R. A1 - Ma, Jia A1 - May, Carrie A. A1 - Maynard, Ernest L. A1 - Modrak-Wojcik, Anna A1 - Mok, Yee-Foong A1 - Mücke, Norbert A1 - Nagel-Steger, Luitgard A1 - Narlikar, Geeta J. A1 - Noda, Masanori A1 - Nourse, Amanda A1 - Obsil, Thomas A1 - Park, Chad K A1 - Park, Jin-Ku A1 - Pawelek, Peter D. A1 - Perdue, Erby E. A1 - Perkins, Stephen J. A1 - Perugini, Matthew A. A1 - Peterson, Craig L. A1 - Peverelli, Martin G. A1 - Piszczek, Grzegorz A1 - Prag, Gali A1 - Prevelige, Peter E. A1 - Raynal, Bertrand D. E. A1 - Rezabkova, Lenka A1 - Richter, Klaus A1 - Ringel, Alison E. A1 - Rosenberg, Rose A1 - Rowe, Arthur J. A1 - Rufer, Arne C. A1 - Scott, David J. A1 - Seravalli, Javier G. A1 - Solovyova, Alexandra S. A1 - Song, Renjie A1 - Staunton, David A1 - Stoddard, Caitlin A1 - Stott, Katherine A1 - Strauss, Holder M. A1 - Streicher, Werner W. A1 - Sumida, John P. A1 - Swygert, Sarah G. A1 - Szczepanowski, Roman H. A1 - Tessmer, Ingrid A1 - Toth, Ronald T. A1 - Tripathy, Ashutosh A1 - Uchiyama, Susumu A1 - Uebel, Stephan F. W. A1 - Unzai, Satoru A1 - Gruber, Anna Vitlin A1 - von Hippel, Peter H. A1 - Wandrey, Christine A1 - Wang, Szu-Huan A1 - Weitzel, Steven E A1 - Wielgus-Kutrowska, Beata A1 - Wolberger, Cynthia A1 - Wolff, Martin A1 - Wright, Edward A1 - Wu, Yu-Sung A1 - Wubben, Jacinta M. A1 - Schuck, Peter T1 - A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation JF - PLoS ONE N2 - Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies. KW - fluorescence-detected sedimentation KW - size exclusion chromatography KW - field flow fractionation KW - spinco ultracentrifuge KW - aggregation KW - bead models KW - velocity KW - hydrodynamics KW - biopharmaceuticals KW - proteins Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151903 VL - 10 IS - 5 ER - TY - JOUR A1 - Lapa, Constantin A1 - Reiter, Theresa A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Werner, Rudolf A. A1 - Pelzer, Theo A1 - Pizarro, Carmen A1 - Skowasch, Dirk A1 - Thomas, Lena A1 - Schlesinger-Irsch, Ulrike A1 - Thomas, Daniel A1 - Bundschuh, Ralph A. A1 - Bauer, Wolfgang R. A1 - Gartner, Florian C. T1 - Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI JF - Oncotarget N2 - Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series. KW - sarcoidosis KW - PET KW - SSTR KW - somatostatin receptor KW - DOTATOC Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175423 VL - 7 IS - 47 ER -