Year: 2020
Type: article
Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium , we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXX trunc ) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXX trunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
Source: Nature Communications
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Stark, Lucy Stebbings, Ólafur Andri Stefánsson, Oliver Stegle, Lincoln D. Stein, Alasdair Stenhouse, Chip Stewart, Stephan Stilgenbauer, Miranda D. Stobbe, Michael R. Stratton, Jonathan R. Stretch, Adam J. Struck, Joshua M. Stuart, Henk G. Stunnenberg, Hong Su, Xiaoping Su, Ren X. Sun, Stephanie Sungalee, Hana Susak, Akihiro Suzuki, Fred Sweep, Monika Szczepanowski, Holger Sültmann, Takashi Yugawa, Angela Tam, David Tamborero, Benita Kiat Tee Tan, Donghui Tan, Patrick Tan, Hiroko Tanaka, Hirokazu Taniguchi, Tomas J. Tanskanen, Maxime Tarabichi, Roy Tarnuzzer, Patrick Tarpey, Morgan L. Taschuk, Kenji Tatsuno, Simon Tavaré, Darrin F. Taylor, Amaro Taylor-Weiner, Jon W. Teague, Bin Tean Teh, Varsha Tembe, Javier Temes, Kevin Thai, Sarah P. Thayer, Nina Thiessen, Gilles Thomas, Sarah Thomas, Alan Thompson, Alastair M. Thompson, John F. F. Thompson, R. Houston Thompson, Heather Thorne, Leigh B. Thorne, Adrian Thorogood, Grace Tiao, Nebojsa Tijanic, Lee E. Timms, Roberto Tirabosco, Marta Tojo, Stefania Tommasi, Christopher W. Toon, Umut H. Toprak, David Torrents, Giampaolo Tortora, Jörg Tost, Yasushi Totoki, David Townend, Nadia Traficante, Isabelle Treilleux, Jean-Rémi Trotta, Lorenz H. P. Trümper, Ming Tsao, Tatsuhiko Tsunoda, Jose M. C. Tubio, Olga Tucker, Richard Turkington, Daniel J. Turner, Andrew Tutt, Masaki Ueno, Naoto T. Ueno, Christopher Umbricht, Husen M. Umer, Timothy J. Underwood, Lara Urban, Tomoko Urushidate, Tetsuo Ushiku, Liis Uusküla-Reimand, Alfonso Valencia, David J. Van Den Berg, Steven Van Laere, Peter Van Loo, Erwin G. Van Meir, Gert G. Van den Eynden, Theodorus Van der Kwast, Naveen Vasudev, Miguel Vazquez, Ravikiran Vedururu, Umadevi Veluvolu, Shankar Vembu, Lieven P. C. Verbeke, Peter Vermeulen, Clare Verrill, Alain Viari, David Vicente, Caterina Vicentini, K. VijayRaghavan, Juris Viksna, Ricardo E. Vilain, Izar Villasante, Anne Vincent-Salomon, Tapio Visakorpi, Douglas Voet, Paresh Vyas, Ignacio Vázquez-García, Nick M. Waddell, Nicola Waddell, Claes Wadelius, Lina Wadi, Rabea Wagener, Jeremiah A. Wala, Jian Wang, Jiayin Wang, Linghua Wang, Qi Wang, Wenyi Wang, Yumeng Wang, Zhining Wang, Paul M. Waring, Hans-Jörg Warnatz, Jonathan Warrell, Anne Y. Warren, Sebastian M. Waszak, David C. Wedge, Dieter Weichenhan, Paul Weinberger, John N. Weinstein, Joachim Weischenfeldt, Daniel J. Weisenberger, Ian Welch, Michael C. Wendl, Johannes Werner, Justin P. Whalley, David A. Wheeler, Hayley C. Whitaker, Dennis Wigle, Matthew D. Wilkerson, Ashley Williams, James S. Wilmott, Gavin W. Wilson, Julie M. Wilson, Richard K. Wilson, Boris Winterhoff, Jeffrey A. Wintersinger, Maciej Wiznerowicz, Stephan Wolf, Bernice H. Wong, Tina Wong, Winghing Wong, Youngchoon Woo, Scott Wood, Bradly G. Wouters, Adam J. Wright, Derek W. Wright, Mark H. Wright, Chin-Lee Wu, Dai-Ying Wu, Guanming Wu, Jianmin Wu, Kui Wu, Yang Wu, Zhenggang Wu, Liu Xi, Tian Xia, Qian Xiang, Xiao Xiao, Rui Xing, Heng Xiong, Qinying Xu, Yanxun Xu, Hong Xue, Shinichi Yachida, Sergei Yakneen, Rui Yamaguchi, Takafumi N. Yamaguchi, Masakazu Yamamoto, Shogo Yamamoto, Hiroki Yamaue, Fan Yang, Huanming Yang, Jean Y. Yang, Liming Yang, Lixing Yang, Shanlin Yang, Tsun-Po Yang, Yang Yang, Xiaotong Yao, Marie-Laure Yaspo, Lucy Yates, Christina Yau, Chen Ye, Kai Ye, Venkata D. Yellapantula, Christopher J. Yoon, Sung-Soo Yoon, Fouad Yousif, Jun Yu, Kaixian Yu, Willie Yu, Yingyan Yu, Ke Yuan, Yuan Yuan, Denis Yuen, Christina K. Yung, Olga Zaikova, Jorge Zamora, Marc Zapatka, Jean C. Zenklusen, Thorsten Zenz, Nikolajs Zeps, Cheng-Zhong Zhang, Fan Zhang, Hailei Zhang, Hongwei Zhang, Hongxin Zhang, Jiashan Zhang, Jing Zhang, Junjun Zhang, Xiuqing Zhang, Xuanping Zhang, Yan Zhang, Zemin Zhang, Zhongming Zhao, Liangtao Zheng, Xiuqing Zheng, Wanding Zhou, Yong Zhou, Bin Zhu, Hongtu Zhu, Jingchun Zhu, Shida Zhu, Lihua Zou, Xueqing Zou, Anna deFazio, Nicholas van As, Carolien H. M. van Deurzen, Marc J. van de Vijver, L. van’t Veer, Christian von Mering
Institutions: German Cancer Research Center, Heidelberg University, National Center for Tumor Diseases, Deutsches Konsortium für Translationale Krebsforschung, Harvard University, University of Cambridge, Peking University, The University of Texas MD Anderson Cancer Center, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Vigo, Ontario Institute for Cancer Research, University of California, Los Angeles, University of Toronto, The University of Melbourne, Peter MacCallum Cancer Centre, Johns Hopkins University, Johns Hopkins Medicine, Sidney Kimmel Comprehensive Cancer Center, Cambridge University Hospitals NHS Foundation Trust, Wellcome Sanger Institute, University of Ottawa, Universitat de Vic - Universitat Central de Catalunya, Barcelona Supercomputing Center, Broad Institute, Cancer Research UK, Quantitative Genomics Medicine Laboratories (qGenomics), Cancer Research UK Cambridge Center, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, The University of Queensland, Institute for Molecular Bioscience, Bar-Ilan University, Yale University, National Institute of Environmental Health Sciences, University of California, Santa Cruz, Brandeis University, Massachusetts General Hospital, New York Genome Center, Hopp Children's Cancer Center Heidelberg, Weill Cornell Medicine, Skolkovo Institute of Science and Technology, Institute for Information Transmission Problems, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Korea Advanced Institute of Science and Technology, Seoul National University Hospital, European Bioinformatics Institute, Seoul National University, Boston Children's Hospital, European Molecular Biology Laboratory, European Molecular Biology Laboratory, Hanyang University, Dana-Farber Cancer Institute, Institute of Medical Science, The University of Tokyo, The University of Tokyo, RIKEN Center for Integrative Medical Sciences, Universitat Pompeu Fabra, University of Tübingen, QIMR Berghofer Medical Research Institute, Washington State University, Beth Israel Deaconess Medical Center, University of Copenhagen, Institució Catalana de Recerca i Estudis Avançats, Charité – Universitätsmedizin Berlin, University of Chicago, National Institutes of Health, National Cancer Institute, University of Helsinki, Memorial Sloan Kettering Cancer Center, Research Center for Advanced Science and Technology, The University of Tokyo, Keimyung University Dongsan Medical Center, Keimyung University Dongsan Hospital, Gachon University, Gachon University Gil Medical Center, Gachon University Medical Center, Hiroshima University, King Faisal Specialist Hospital & Research Centre, Spanish National Cancer Research Centre, University Medical Center Hamburg-Eppendorf, Leibniz Institute of Virology (LIV), Center for Cancer Research, BC Cancer Agency, Canada's Michael Smith Genome Sciences Centre, University of California San Diego, Moores Cancer Center, Royal National Orthopaedic Hospital, Baylor College of Medicine, The Jackson Laboratory for Genomic Medicine, Universität Ulm, Christian-Albrechts-Universität zu Kiel, Salford Royal NHS Foundation Trust, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Oregon Health & Science University, OHSU Knight Cancer Institute, Washington University in St. Louis, University College London, National Cancer Centre Japan, National Cancer Center Research Institute, Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR), Tokyo Women's Medical University, Los Alamos National Laboratory, University Health Network, Nottingham University Hospitals NHS Trust, Toronto General Hospital, University of North Carolina at Chapel Hill, Vector Institute, UNC Lineberger Comprehensive Cancer Center, Oslo University Hospital, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of Glasgow, Alvin J. Siteman Cancer Center, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, University of Leeds, St James's University Hospital, Princess Alexandra Hospital, University Hospitals Cleveland Medical Center, Case Western Reserve University, Gloucestershire Royal Hospital, University of Calgary, Royal Stoke University Hospital, University Hospital Southampton NHS Foundation Trust, Human Longevity (United States), La Trobe University, Olivia Newton-John Cancer Research Institute, Chinese Academy of Sciences, Computer Network Information Center, Genome Canada, Buck Institute for Research on Aging, Duke Medical Center, Medizinische Hochschule Hannover, Cedars-Sinai Medical Center, Queen Mary University of London, Barts Cancer Institute, Hebrew University of Jerusalem, Leipzig University, University of Southern California, USC Norris Comprehensive Cancer Center, Aarhus University, Instituto Carlos Slim de la Salud, Aarhus University Hospital, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Garvan Institute of Medical Research, Glasgow Royal Infirmary, UNSW Sydney, The Kinghorn Cancer Centre, National Institute of Biomedical Genomics, University of Oslo, Institute of Cancer Research, Duke-NUS Medical School, Lund University, Heinrich Heine University Düsseldorf, Friedrich-Ebert-Krankenhaus, University of Oxford, McGill University, Tampere University, Tampere University Hospital, Leeds Teaching Hospitals NHS Trust, Centre Léon Bérard, Fox Chase Cancer Center, Centre international de recherche sur le cancer, University of East Anglia, Earlham Institute, Radboud University Nijmegen, Radboud Institute for Molecular Life Sciences, Brigham and Women's Hospital, Princess Margaret Cancer Centre, University of Manchester, Cancer Research UK Manchester Centre, The Netherlands Cancer Institute, Oncode Institute, Novo Nordisk Foundation, Technical University of Denmark, Bundesministerium für Forschung, Technologie und Raumfahrt, The University of Sydney, Melanoma Institute Australia, University Hospital Münster, Stanford Medicine, Stanford University, Foundation Medicine (United States), University of California, San Francisco, Royal Marsden NHS Foundation Trust, Institut Gustave Roussy, Ministerio de Ciencia, Innovación y Universidades, U-M Rogel Cancer Center, University of Bern, University Hospital of Bern, University of Pavia, University of Alabama at Birmingham, Icahn School of Medicine at Mount Sinai, University of Tasmania, Centre for Law and Genetics, Mayo Clinic, Division of Cancer Epidemiology and Genetics, Wollongong Hospital, Illawarra Shoalhaven Local Health District, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Biologie intégrée pour la valorisation de la diversité des arbres et de la forêt, Westmead Hospital, Westmead Institute for Medical Research, Electronics and Telecommunications Research Institute, Institut National du Cancer, National Cancer Centre Singapore, University Hospital Schleswig-Holstein, University of Auckland, Royal Children's Hospital, Walter and Eliza Hall Institute of Medical Research, Murdoch Children's Research Institute, Vancouver Prostate Centre, Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, Victorian Institute of Forensic Medicine, Norfolk and Norwich University Hospital, University of Cologne, International Genomics Consortium, Children's Hospital at Westmead, Barking, Havering And Redbridge University Hospitals NHS Trust, SIB Swiss Institute of Bioinformatics, ETH Zurich, MRC Cancer Unit, Seven Bridges Genomics (United States), Addenbrooke's Hospital, University of Padua, University of Geneva, University of Lausanne, The Francis Crick Institute, Genome Institute of Singapore, KU Leuven, National University of Singapore, Institut Jules Bordet, Institute for Research in Biomedicine, Shadyside Hospital, University of Pittsburgh Medical Center, Uppsala University, Science for Life Laboratory, Hefei University of Technology, University of Antwerp, GZA Ziekenhuizen Campus Sint-Augustinus, GZA Ziekenhuizen, Simon Fraser University, University of Pennsylvania, Wellcome Trust, Hospital for Sick Children, Queen Elizabeth University Hospital, Prostate Cancer Canada, Medicon Village, Universitat de Girona, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Icelandic Cancer Society, Xijing Hospital, State Key Laboratory of Cancer Biology, Air Force Medical University, Rigshospitalet, Australian Institute of Tropical Health and Medicine, Université de Montréal, James Cook University, Fondazione IRCCS Istituto Neurologico Carlo Besta, Bioplatforms Australia, Erasmus MC, Erasmus MC Cancer Institute, Prince Charles Hospital, University of Liverpool, Universidade do Porto, Centro de Investigação em Biodiversidade e Recursos Genéticos, University of Florida Health, University of Florida, University of Milano-Bicocca, BGI Group (China), University of Würzburg, University of Miami, Sylvester Comprehensive Cancer Center, St Thomas' Hospital, Municipal Institute for Medical Research, Hospital del Mar Research Institute, Osaka International Cancer Institute, Skåne University Hospital, Beatson West of Scotland Cancer Centre, National Human Genome Research Institute, Victorian Comprehensive Cancer Centre, German Center for Infection Research, Government of India, Department of Biotechnology, Ministry of Science and Technology, University of British Columbia, The University of Texas Health Science Center at Houston, Imperial College London, Goethe University Frankfurt, University Hospital Frankfurt, UC San Diego Health System, Oxford Nanopore Technologies (United Kingdom), Howard Hughes Medical Institute, Wakayama Medical University, Salford Royal Hospital, University of Tennessee Health Science Center, Center for Life Sciences, Children's Hospital of Philadelphia, Karolinska Institutet, Donnelly Centre for Cellular and Biomolecular Research, Hallym University, Institut de Biologia Evolutiva, Hokkaido University, National Cancer Center Hospital, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), University of Nebraska Medical Center, Amsterdam UMC Location University of Amsterdam, China National GeneBank, Hong Kong University of Science and Technology, Xi'an Jiaotong University, AbbVie (United States), Edinburgh Royal Infirmary, Max Delbrück Center, University Hospital Heidelberg, Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Johns Hopkins Hospital, Michael E. DeBakey VA Medical Center, Asan Medical Center, University of Ulsan, Endeavor Health, University of Ljubljana, McGill University and Génome Québec Innovation Centre, University Hospital Zurich, Institute of Genetics and Cancer, MRC Human Genetics Unit, University of Edinburgh, University of Zurich, University of Zagreb, South Australia Pathology, George Washington University, Macquarie University, MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Royal Prince Alfred Hospital, Khon Kaen University, National Cancer Center, Ewha Womans University, Sungkyunkwan University, Dana-Farber Brigham Cancer Center, University of Bergen, Institute of Computer Science, Polish Academy of Sciences, University of Göttingen, University of Duisburg-Essen, Van Andel Institute, King's College London, Guy's and St Thomas' NHS Foundation Trust, Royal Brisbane and Women's Hospital, University of Gothenburg, Children's Medical Research Institute, Institute of Biomedical Sciences, Academia Sinica, Academia Sinica, Max Planck Institute for Molecular Genetics, Biobyte Solutions (Germany), NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Leidos Biomedical Research Inc. (United States), Second Military Medical University, Peking University Cancer Hospital, Beijing Hospital, University of St Andrews, Institute for Systems Biology, Universidad de Oviedo, Institut Bergonié, Children's Hospital Los Angeles, Australian National University, Ghent University, Nationwide Children's Hospital, Duke University, Universitat Autònoma de Barcelona, Institut Català de Paleontologia Miquel Crusafont, University of California, Davis, Western Sydney University, Henry Ford Hospital, Kyushu University, Heidelberg Academy of Sciences and Humanities, Roswell Park Comprehensive Cancer Center, Penrose-St. Francis Health Services, University Hospital Ulm, German Cancer Aid, Chinese University of Hong Kong, St. Jude Children's Research Hospital, Carleton College, HudsonAlpha Institute for Biotechnology, O'Neal Comprehensive Cancer Center, Keio University, Sage Bionetworks, Robert Bosch Hospital, National Cancer Center Hospital, Samsung Medical Center, Sangmyung University, NYU Langone Health, Cleveland Clinic, Christiana Care Health System, SRA International (United States), Guy's Hospital, Kings Health Partners, Inserm, Centre Hospitalier Universitaire de Besançon, Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, Institutul Clinic Fundeni, Royal Surrey County Hospital, Royal Surrey NHS Foundation Trust, National Institute for Health and Care Research, NIHR Cambridge Biomedical Research Centre, Ninewells Hospital, Medical College of Wisconsin, Winship Cancer Institute, Princeton University, Vanderbilt University, Vanderbilt-Ingram Cancer Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Yokohama City University, Universitätsklinikum Gießen und Marburg, Institut Regional du Cancer de Montpellier, North Bristol NHS Trust, SingHealth, National Heart Centre Singapore, Weill Cornell Medical Center, Vall d'Hebron Institute of Oncology, Tata Institute of Fundamental Research, National Centre for Biological Sciences, Indiana University Bloomington, Indiana University, Analytical Biological Services (United States), Tata Memorial Hospital, Advanced Centre for Treatment, Research and Education in Cancer, University of Newcastle Australia, Essen University Hospital, Martini-Klinik, University of Pittsburgh, Massachusetts Eye and Ear Infirmary, Japan Agency for Medical Research and Development, Korea University, Walter Reed National Military Medical Center, University Hospitals Coventry and Warwickshire NHS Trust, Radboud University Medical Center, Sankt-Antonius-Hospital Eschweiler, University of Iceland, Institut Curie, Singapore General Hospital, Cancer Science Institute of Singapore, Columbia University, Institute of Molecular and Cell Biology, Istituto Tumori Bari, Agostino Gemelli University Polyclinic, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Maastricht University, Care and Public Health Research Institute, Lyon 1 Université, Tokyo Medical and Dental University, Japan Science and Technology Agency, University Hospitals Birmingham NHS Foundation Trust, Queen's University Belfast, University of Southampton, Tallinn University of Technology, Sickkids Research Institute, Emory University, Norwegian University of Science and Technology, IMEC, John Radcliffe Hospital, UL Institute of Mathematics and Computer Science, University of Latvia, Augusta University, Wythenshawe Hospital, Leibniz Institute for Baltic Sea Research Warnemünde, Centre for Human Genetics, Poznan University of Medical Sciences, International Institute for Molecular Oncology, MRC University of Glasgow Centre for Virus Research, Huazhong University of Science and Technology, The University of Osaka, First Affiliated Hospital of Xi'an Jiaotong University, Shanghai Jiao Tong University, Ruijin Hospital, Epworth Hospital, Monash University, Northwestern University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: G1193327600, G1953887145, Pan-cancer functional evaluation of non-coding DNA mutations, G386869943, G4307269042, G434337789, G4799834350, Analysis of BRCA1 recombination functions, Internationales Krebsgenomkonsortium (ICGC): Die Genome von früh entstehenden Prostatatumoren, Arbeitspaket 1, 5, 6, 7 und 8, ICGC-Data Mining: Charakterisierung des nicht-Protein-kodierenden Subgenoms in Tumorzellen, Standort Heidelberg DKFZ, Mechanisms of genome instability induced by APOBEC Cytidine Deaminases and its impacts during cancer development., G7812574996, G7884127298, G8241103651, FANCM in repair of stalled replication forks, Cancer Center Support Grant, UNC Center for Environmental Health and Susceptibility, DNA damage response and repair of a broken chromosome, G923755333, G950849122
OpenAlex ID: W3005477834