Published in
Nature Research, Nature Communications, 1(11), 2020
DOI: 10.1038/s41467-019-13824-9
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Genomic footprints of activated telomere maintenance mechanisms in cancer
Journal article published in 2017 by
Ruibin Xi,
Fan Zhang,
Hailei Zhang,
Hongwei Zhang,
Hongxin Zhang,
Jiashan Zhang,
Jing Zhang,
Junjun Zhang,
Xiuqing Zhang,
Xuanping Zhang,
Yan Zhang,
Zemin Zhang,
Christof von Kalle,
Zhongming Zhao,
Liangtao Zheng
and other authors.
Ruibin Xi,
Fan Zhang,
Hailei Zhang,
Hongwei Zhang,
Hongxin Zhang,
Jiashan Zhang,
Jing Zhang,
Junjun Zhang,
Xiuqing Zhang,
Xuanping Zhang,
Yan Zhang,
Zemin Zhang,
Christof von Kalle,
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,
Yussanne,
Shanlin Yang,
Tsun-Po Yang,
Yang Yang,
Lixing Yang,
Sung-Soo Yoon,
Lina Sieverling 
,
Peter J. Park,
Jake June-Koo Lee,
Kin Chan,
Ken Chen,
Isidro Cortés-Ciriano,
Steven A. Roberts,
Chen Hong,
Barbara Hutter,
David T. W. Jones,
Eunjung Alice Lee,
Sandra D. Koser,
Yilong Li,
Fabio C. P. Navarro,
Sultan T. Al-Sedairy,
Nicola D. Roberts,
Bernardo Rodriguez-Martin,
J. Lynn Fink,
Nicola Waddell,
Philip Ginsbach,
J. Todd Auman,
Hikmat Al-Ahmadie,
Fatima Al-Shahrour,
Malik Alawi,
Monique Albert,
Kenneth Aldape,
Kadir C. Akdemir,
Ludmil B. Alexandrov,
Adrian Ally,
Kathryn Alsop,
Fernanda Amary,
Samirkumar B. Amin,
Brice Aminou,
Ole Ammerpohl,
Matthew J. Anderson,
Eva G. Alvarez,
Yeng Ang,
Davide Antonello,
Pavana Anur,
Samuel Aparicio,
Elizabeth L. Appelbaum,
Yasuhito Arai,
Axel Aretz,
Koji Arihiro,
Adrian Baez-Ortega,
Shun-Ichi Ariizumi,
Joshua Armenia,
Laurent Arnould,
Sylvia Asa,
Kortine Kleinheinz,
Yassen Assenov,
R. Xi,
Gurnit Atwal,
Sietse Aukema,
Rameen Beroukhim,
Miriam R. R. Aure,
Philip Awadalla,
Sultan T. Al Sedairy,
Marta Aymerich,
Gary D. Bader,
Matthew H. Bailey,
Peter J. Bailey,
Miruna Balasundaram,
Paul C. Boutros,
Saianand Balu,
Pratiti Bandopadhayay,
Rosamonde E. Banks,
Stefano Barbi,
Andrew P. Barbour,
Jonathan Barenboim,
Jill Barnholtz-Sloan,
David D. L. Bowtell,
Hugh Barr,
Elisabet Barrera,
John Bartlett,
Javier Bartolome,
Claudio Bassi,
Delia M. Braun,
Oliver F. Bathe,
Daniel Baumhoer,
Prashant Bavi,
Stephen B. Baylin,
Wojciech Bazant,
Duncan Beardsmore,
P. J. Park,
Timothy A. Beck,
Sam Behjati,
Andreas Behren,
Beifang Niu,
Cindy Bell,
Kathleen H. Burns,
J. Todd Auman,
Sergi Beltran,
Christopher Benz,
Andrew Berchuck,
Anke K. Bergmann,
Erik N. Bergstrom,
G. Steven Bova,
Benjamin P. Berman,
Peter J. Campbell,
Daniel M. Berney,
R. Eils,
Stephan H. Bernhart,
Benedikt Brors,
Mario Berrios,
Samantha Bersani,
Johanna Bertl,
Miguel Betancourt,
Vinayak Bhandari,
Shriram G. Bhosle,
Andrew V. Biankin,
Matthias Bieg,
Darell Bigner,
Hans Binder,
Ewan Birney,
Michael Birrer,
Nidhan K. Biswas,
Bodil Bjerkehagen,
Tom Bodenheimer,
Lori Boice,
Giada Bonizzato,
Johann S. De Bono,
Arnoud Boot,
Moiz S. Bootwalla,
Ake Borg,
Arndt Borkhardt,
Keith A. Boroevich,
Ana Dueso-Barroso,
Ivan Borozan,
Roland Eils,
Christoph Borst,
Marcus Bosenberg,
Mattia Bosio,
Jacqueline Boultwood,
Guillaume Bourque,
Andrew J. Dunford,
David T. Bowen,
Reanne Bowlby,
Sandrine Boyault,
Rich Boyce,
Jeffrey Boyd,
Alvis Brazma,
Paul Brennan,
Daniel S. Brewer,
Paul A. Edwards,
Arie B. Brinkman,
Isidro Cortes-Ciriano ,
Robert G. Bristow,
Russell R. Broaddus,
Jane E. Brock,
Malcolm Brock,
Annegien Broeks,
Angela N. Brooks,
Denise Brooks,
Søren Brunak,
Xavier Estivill,
Timothy J. C. Bruxner,
Alicia L. Bruzos,
Alex Buchanan,
J. Lynn Fink,
Ivo Buchhalter,
Christiane Buchholz,
Susan Bullman,
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Adam P. Butler,
Atul J. Butte,
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Elias Campo,
Lars Feuerbach,
Cinzia Cantù,
Shaolong Cao,
Thomas E. Carey,
Joana Carlevaro-Fita,
Rebecca Carlsen,
Milana Frenkel-Morgenstern,
Ivana Cataldo,
Mario Cazzola,
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Dimple Chakravarty,
Don Chalmers,
Dale W. Garsed,
Calvin Wing Yiu Chan,
Michelle Chan-Seng-Yue,
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Koser Sd,
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Lorraine A. Chantrill,
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Hsiao-Wei Chen,
Jieming Chen,
Andrew D. Cherniack,
Jeremy Chien,
Yoke-Eng Chiew,
Suet-Feung Chin,
Dmitry A. Gordenin,
Juok Cho,
Sunghoon Cho,
Jung Kyoon Choi,
Wan Choi,
Christine Chomienne,
Zechen Chong,
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David Haan,
Angela Chou,
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Shuai Ding,
Huy Q. Dinh,
Luc Dirix,
HarshaVardhan Doddapaneni,
Nilgun Donmez,
Matthias Schlesner ,
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German Ott,
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Joong-Won Park,
Keunchil Park,
Kiejung Park,
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Paolo Pederzoli,
Martin Peifer,
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Charles M. Perou,
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Myron Peto,
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Andreia V. Pinho,
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Elena Piñeiro-Yáñez,
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Tirso Pons,
Irinel Popescu,
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Aparna Prasad,
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Manuel Prinz,
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Petar Radovic,
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Kamna Ramakrishnan,
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and the Icgc/Tcga Pan-Cancer Analysis of Whole Genomes Network
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Jake June-Koo Lee,
Kin Chan,
Ken Chen,
Isidro Cortés-Ciriano,
Steven A. Roberts,
Chen Hong,
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Yu Fan,
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Taobo Hu,
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Mei Huang,
Mi Ni Huang,
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Sinisa Ivkovic,
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Umut H. Toprak,
Giampaolo Tortora,
Jörg Tost,
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David Townend,
Nadia Traficante,
Isabelle Treilleux,
Jean-Rémi Trotta,
Lorenz H. P. Trümper,
Ming Tsao,
Tatsuhiko Tsunoda,
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,
R. Houston Thompson,
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,
Anne Vincent-Salomon,
Tapio Visakorpi,
Douglas Voet,
Paresh Vyas,
Ignacio Vázquez-García,
Claes Wadelius,
Lina Wadi,
Rabea Wagener,
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,
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,
K. C. Akdemir,
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,
H. Al Ahmadie,
and the Icgc/Tcga Pan-Cancer Analysis of Whole Genomes Network
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Abstract
AbstractCancers 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/DAXXtrunc) 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/DAXXtrunc 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.