Pervasive chromosomal instability and karyotype order in tumour evolution.
Thomas B.K. Watkins,Emilia L. Lim,Emilia L. Lim,Marina Petkovic,Sergi Elizalde,Nicolai Juul Birkbak,Nicolai Juul Birkbak,Nicolai Juul Birkbak,Gareth A. Wilson,David Allan Moore,Eva Grönroos,Andrew Rowan,Sally M. Dewhurst,Jonas Demeulemeester,Jonas Demeulemeester,Stefan C. Dentro,Stefan C. Dentro,Stefan C. Dentro,Stuart Horswell,Lewis Au,Lewis Au,Kerstin Haase,Mickael Escudero,Rachel Rosenthal,Rachel Rosenthal,Maise Al Bakir,Hang Xu,Kevin Litchfield,Wei-Ting Lu,Thanos P. Mourikis,Michelle Dietzen,Lavinia Spain,Lavinia Spain,George D. Cresswell,Dhruva Biswas,Dhruva Biswas,Philippe Lamy,Iver Nordentoft,Katja Harbst,Francesc Castro-Giner,Francesc Castro-Giner,Lucy R. Yates,Lucy R. Yates,Franco Caramia,Fanny Jaulin,Cecile Vicier,Ian Tomlinson,Priscilla K. Brastianos,Priscilla K. Brastianos,Raymond J. Cho,Boris C. Bastian,Lars Dyrskjøt,Göran Jönsson,Peter Savas,Peter Savas,Sherene Loi,Sherene Loi,Peter J. Campbell,Fabrice Andre,Fabrice Andre,Nicholas M. Luscombe,Nicholas M. Luscombe,Nicholas M. Luscombe,Neeltje Steeghs,Vivianne C. G. Tjan-Heijnen,Zoltan Szallasi,Zoltan Szallasi,Samra Turajlic,Samra Turajlic,Mariam Jamal-Hanjani,Peter Van Loo,Samuel F. Bakhoum,Roland F. Schwarz,Roland F. Schwarz,Nicholas McGranahan,Charles Swanton,Charles Swanton +76 more
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TLDR
Multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types are used to show that continuous chromosomal instability results in pervasive SCNA heterogeneity.Abstract:
Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2+ breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.read more
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Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Kevin Litchfield,Kevin Litchfield,James L. Reading,Clare Puttick,Krupa Thakkar,Krupa Thakkar,Christopher Abbosh,Robert B Bentham,Thomas B.K. Watkins,Rachel Rosenthal,Dhruva Biswas,Andrew Rowan,Emilia L. Lim,Maise Al Bakir,Virginia Turati,José Afonso Guerra-Assunção,Lucia Conde,Andrew Furness,Sunil Kumar Saini,Sine Reker Hadrup,Javier Herrero,Se-Hoon Lee,Se-Hoon Lee,Peter Van Loo,Tariq Enver,James Larkin,Matthew D. Hellmann,Samra Turajlic,Samra Turajlic,Sergio A. Quezada,Nicholas McGranahan,Charles Swanton,Charles Swanton +32 more
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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
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TL;DR: In this article, the authors extensively characterize intra-tumor heterogeneity (ITH) across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations.
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Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients
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Journal ArticleDOI
Genetic and non-genetic clonal diversity in cancer evolution.
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Field,Anna Fitzgerald,Peter Hersey,Valerie Jakrot,Peter Johansson,Hojabr Kakavand,Richard F. Kefford,Loretta Lau,Georgina V. Long,Hilda A. Pickett,Antonia L. Pritchard,Gulietta M. Pupo,Robyn P. M. Saw,Sarah-Jane Schramm,Catherine A. Shang,Ping Shang,Andrew J. Spillane,Jonathan R. Stretch,Varsha Tembe,John F. Thompson,Ricardo E. Vilain,James S. Wilmott,Jean Y. Yang,Nicholas K. Hayward,Graham J. Mann,Richard A. Scolyer,John M. S. Bartlett,Prashant Bavi,Dianne Chadwick,Michelle Chan-Seng-Yue,Sean P. Cleary,Ashton A. Connor,Karolina Czajka,Robert E. Denroche,Neesha C. Dhani,Jenna Eagles,Steven Gallinger,Robert C. Grant,David W. Hedley,Michael A. Hollingsworth,Gun Ho Jang,Jeremy Johns,Sangeetha N Kalimuthu,Sheng-Ben Liang,Ilinca Lungu,Xuemei Luo,Faridah Mbabaali,Treasa McPherson,Jessica Miller,Malcolm J. Moore,Faiyaz Notta,Danielle Pasternack,Gloria M. Petersen,Michael H.A. Roehrl,Michelle Sam,Iris Selander,Stefano Serra,Sagedeh Shahabi,Sarah P. Thayer,Lee Timms,Gavin W. Wilson,Julie M. Wilson,Bradly G. Wouters,John Douglas Mcpherson,Timothy A. Beck,Vinayak Bhandari,Colin Collins,Neil Fleshner,Natalie S. Fox,Michael Fraser,Lawrence E. Heisler,Emilie Lalonde,Julie Livingstone,Alice Meng,Veronica Y. Sabelnykova,Yu-Jia Shiah,Theodorus van der Kwast,Robert G. Bristow,Shuai Ding,Daiming Fan,Lin Li,Yongzhan Nie,Xiao Xiao,Rui Xing,Shanlin Yang,Yingyan Yu,Yong Zhou,Rosamonde E. Banks,Guillaume Bourque,Paul Brennan,Louis Letourneau,Yasser Riazalhosseini,Ghislaine Scelo,Naveen S. Vasudev,Juris Viksna,Mark Lathrop,Jörg Tost,Sung-Min Ahn,Samuel Aparicio,Laurent Arnould,Miriam Ragle Aure,Shriram G. Bhosle,Ewan Birney,Åke Borg,Sandrine Boyault,Arie B. Brinkman,Jane E. Brock,Annegien Broeks,Anne Lise Børresen-Dale,Carlos Caldas,Suet-Feung Chin,Helen Davies,Christine Desmedt,Luc Dirix,Serge Dronov,Anna Ehinger,Jorunn E. Eyfjord,Aquila Fatima,John A. Foekens,P. A. Futreal,Øystein Garred,Dilip Giri,Dominik Glodzik,Dorthe Grabau,Holmfridur Hilmarsdottir,Gerrit K. J. Hooijer,Jocelyne Jacquemier,Se Jin Jang,Jon G. Jonasson,J Jonkers,Hyung-Yong Kim,Tari A. King,Stian Knappskog,Gu Kong,Savitri Krishnamurthy,Sunil R. Lakhani,Anita Langerød,Denis Larsimont,Hee Jin Lee,Jeong-Yeon Lee,Ming Ta Michael Lee,Ole Christian Lingjærde,Gaëtan MacGrogan,John W.M. Martens,Sarah O’Meara,Iris Pauporté,Sarah E Pinder,Xavier Pivot,Elena Provenzano,Colin A. Purdie,Manasa Ramakrishna,Kamna Ramakrishnan,Jorge S. Reis-Filho,Andrea L. Richardson,Markus Ringnér,Javier Bartolome Rodriguez,F. Germán Rodríguez-González,Gilles Romieu,Roberto Salgado,Torill Sauer,Rebecca Shepherd,Anieta M. Sieuwerts,Peter T. Simpson,Marcel Smid,Christos Sotiriou,Paul N. Span,Olafur A. Stefansson,Alasdair Stenhouse,Henk Stunnenberg,Fred C.G.J. Sweep,Benita Kiat Tee Tan,Gilles Thomas,Alastair M. Thompson,Stefania Tommasi,Isabelle Treilleux,Andrew Tutt,Naoto T. Ueno,Steven Van Laere,Gert Van den Eynden,Peter Vermeulen,Alain Viari,Anne Vincent-Salomon,Bernice H. Wong,Lucy R. Yates,Xueqing Zou,Carolien H.M. van Deurzen,Marc J. van de Vijver,Laura J. van't Veer,Ole Ammerpohl,Sietse M. Aukema,Anke K. Bergmann,Stephan H. Bernhart,Arndt Borkhardt,Christoph Borst,Birgit Burkhardt,Alexander Claviez,Maria Elisabeth Goebler,Andrea Haake,Siegfried Haas,Martin L. Hansmann,Jessica I. Hoell,Michael Hummel,Dennis Karsch,Wolfram Klapper,Michael Kneba,Markus Kreuz,Dieter Kube,Ralf Kueppers,Dido Lenze,Markus Loeffler,Cristina López,Luisa Mantovani-Loeffler,Peter Moeller,German Ott,Bernhard Radlwimmer,Julia Richter,Marius Rohde,Philip Rosenstiel,Andreas Rosenwald,Markus Schilhabel,Stefan Schreiber,Peter F. Stadler,Peter Staib,Stephan Stilgenbauer,Stephanie Sungalee,Monika Szczepanowski,Umut H. Toprak,Lorenz Truemper,Rabea Wagener,Thorsten Zenz,Volker Hovestadt,Christof von Kalle,Marcel Kool,Andrey Korshunov,Pablo Landgraf,Hans Lehrach,Paul A. Northcott,Stefan M. Pfister,Guido Reifenberger,Hans-Joerg Warnatz,Stephan Wolf,Marie-Laure Yaspo,Yassen Assenov,Clarissa Gerhäuser,Sarah Minner,Thorsten Schlomm,Ronald Simon,Guido Sauter,Holger Sueltmann,Nidhan K. Biswas,Arindam Maitra,Partha P. Majumder,Rajiv Sarin,Stefano Barbi,Giada Bonizzato,Cinzia Cantù,Angelo Paolo Dei Tos,Matteo Fassan,Sonia Grimaldi,Claudio Luchini,Giuseppe Malleo,Giovanni Marchegiani,Michele Milella,Salvatore Paiella,Antonio Pea,Paolo Pederzoli,Andrea Ruzzenente,Roberto Salvia,Nicola Sperandio,Yasuhito Arai,Natsuko Hama,Nobuyoshi Hiraoka,Fumie Hosoda,Hiromi Nakamura,Hidenori Ojima,Takuji Okusaka,Yasushi Totoki,Tomoko Urushidate,Masashi Fukayama,Shumpei Ishikawa,Hitoshi Katai,Hiroto Katoh,Daisuke Komura,Hirofumi Rokutan,Mihoko Saito-Adachi,Akihiro Suzuki,Hirokazu Taniguchi,Kenji Tatsuno,Tetsuo Ushiku,Shinichi Yachida,Shogo Yamamoto,Hiroshi Aikata,Koji Arihiro,Shunichi Ariizumi,Kazuaki Chayama,Mayuko Furuta,Kunihito Gotoh,Shinya Hayami,Satoshi Hirano,Yoshiiku Kawakami,Kazuhiro Maejima,Toru Nakamura,Kaoru Nakano,Hideki Ohdan,Aya Sasaki-Oku,Hiroko Tanaka,Masaki Ueno,Masakazu Yamamoto,Hiroki Yamaue,Su Pin Choo,Ioana Cutcutache,Narong Khuntikeo,Choon Kiat Ong,Chawalit Pairojkul,Irinel Popescu,Keun Soo Ahn,Marta Aymerich,Armando López-Guillermo,Carlos López-Otín,Xose S. Puente,Elias Campo,Fernanda Amary,Daniel Baumhoer,Sam Behjati,Bodil Bjerkehagen,Ola Myklebost,Nischalan Pillay,P. S. Tarpey,Roberto Tirabosco,Olga Zaikova,Adrienne M. Flanagan,Jacqueline Boultwood,David T. Bowen,Mario Cazzola,Anthony R. Green,Eva Hellström-Lindberg,Luca Malcovati,Jyoti Nangalia,Elli Papaemmanuil,Paresh Vyas,Yeng Ang,Hugh Barr,Duncan Beardsmore,Matthew D. Eldridge,James A. Gossage,Nicola Grehan,George B. Hanna,Stephen J. Hayes,Ted R. Hupp,David Khoo,Jesper Lagergren,Laurence Lovat,Shona MacRae,Maria O'Donovan,J. Robert O’Neill,Simon L. Parsons,Shaun R. Preston,Sonia Puig,Tom Roques,Grant Sanders,Sharmila Sothi,Simon Tavaré,Olga Tucker,Richard C. Turkington,Timothy J. Underwood,Ian Welch,Rebecca C. Fitzgerald,Daniel M. Berney,Johann S. De Bono,Declan Cahill,Niedzica Camacho,Nening Dennis,Tim Dudderidge,S. Edwards,Cyril Fisher,Christopher S. Foster,Mohammed J. R. Ghori,Pelvender Gill,Vincent J. Gnanapragasam,Gunes Gundem,Freddie C. Hamdy,Steve Hawkins,Steven Hazell,William J. Howat,William B. Isaacs,Katalin Karaszi,Jonathan D. Kay,Vincent Khoo,Z Kote-Jarai,Barbara Kremeyer,Pardeep Kumar,Adam Lambert,D. Leongamornlert,Naomi Livni,Yong-Jie Lu,Hayley J. Luxton,Luke Marsden,Charles E. Massie,Lucy Matthews,Erik Mayer,Ultan McDermott,Sue Merson,David E. Neal,Anthony C. H. Ng,David Nicol,Chris Ogden,Edward Rowe,Nimish Shah,Sarah Thomas,Alan Thompson,Clare Verrill,Tapio Visakorpi,Anne Y. Warren,Hayley C. Whitaker,Hongwei Zhang,Nicholas van As,Rosalind A. Eeles,Adam Abeshouse,Nishant Agrawal,Rehan Akbani,Hikmat Al Ahmadie,Monique Albert,Kenneth Aldape,Adrian Ally,Elizabeth L. Appelbaum,Joshua Armenia,Sylvia L. Asa,J. Todd Auman,Miruna Balasundaram,Saianand Balu,Jill S. Barnholtz-Sloan,Oliver F. Bathe,Stephen B. Baylin,Christopher C. Benz,Andrew Berchuck,Mario Berrios,Darell D. Bigner,Michael Birrer,Tom Bodenheimer,Lori Boice,Moiz S. Bootwalla,Marcus Bosenberg,Reanne Bowlby,Jeff Boyd,Russell R. Broaddus,Malcolm V. Brock,Denise Brooks,Susan Bullman,Samantha J. Caesar-Johnson,Thomas E. Carey,Rebecca Carlsen,Robert J. Cerfolio,Vishal S. Chandan,Hsiao-Wei Chen,Andrew D. Cherniack,Jeremy Chien,Juok Cho,Eric Chuah,Carrie Cibulskis,Leslie Cope,Matthew G. Cordes,Erin Curley,Bogdan Czerniak,Ludmila Danilova,Ian J. Davis,Timothy Defreitas,John A. Demchok,Noreen Dhalla,Rajiv Dhir,Harshavardhan Doddapaneni,Adel K. El-Naggar,Ina Felau,Martin L. Ferguson,Gaetano Finocchiaro,Kwun M. Fong,Scott Frazer,William A. Friedman,Catrina C. Fronick,Lucinda Fulton,Stacey Gabriel,Jianjiong Gao,Nils Gehlenborg,Jeffrey E. Gershenwald,Ronald Ghossein,Nasra H. Giama,Richard A. Gibbs,Carmen Gomez,Ramaswamy Govindan,D. Neil Hayes,Apurva M. Hegde,David I. Heiman,Zachary J. Heins,Austin J. Hepperla,Andrea Holbrook,Robert A. Holt,Alan P. Hoyle,Ralph H. Hruban,Jianhong Hu,Mei Huang,David G. Huntsman,Jason T. Huse,Christine A. Iacobuzio Donahue,Michael Ittmann,Joy Jayaseelan,Stuart R. Jefferys,Corbin D. Jones,Steven J.M. Jones,Hartmut Juhl,Koo Jeong Kang,Beth Y. Karlan,Katayoon Kasaian,Electron Kebebew,Hark Kyun Kim,Viktoriya Korchina,Ritika Kundra,Phillip H. Lai,Eric S. Lander,Xuan Le,Darlene Lee,Douglas A. Levine,Lora Lewis,Tim Ley,Haiyan Irene Li,Pei Lin,W. M. Linehan,Fei-Fei Liu,Yiling Lu,Lisa Lype,Yussanne Ma,Dennis T. Maglinte,Elaine R. Mardis,Jeffrey R. Marks,Marco A. Marra,Thomas Matthew,Michael Mayo,Karen K. Smith McCune,Sam Meier,Shaowu Meng,Piotr A. Mieczkowski,Tom Mikkelsen,Christopher A. Miller,Gordon B. Mills,Richard A. Moore,Carl Morrison,Lisle E. Mose,Catherine D. Moser,Andrew J. Mungall,Karen Mungall,David G. Mutch,Donna Muzny,Jerome Myers,Yulia Newton,Michael S. Noble,Peter H. O'Donnell,Brian P. O'Neill,Angelica Ochoa,Joong-Won Park,Joel S. Parker,Harvey I. Pass,Alessandro Pastore,Nathan A. Pennell,Charles M. Perou,Nicholas J. Petrelli,Olga Potapova,Janet S. Rader,Suresh S. Ramalingam,W. Kimryn Rathmell,Victor E. Reuter,Sheila Reynolds,Matthew D. Ringel,Jeffrey Roach,Lewis R. Roberts,A. Gordon Robertson,Sara Sadeghi,Charles Saller,Francisco Sanchez-Vega,Dirk Schadendorf,Jacqueline E. Schein,Heather K. Schmidt,Nikolaus Schultz,Raja R. Seethala,Yasin Senbabaoglu,Troy Shelton,Yan Shi,Juliann Shih,Ilya Shmulevich,Craig D. Shriver,Sabina Signoretti,Janae V. Simons,Samuel Singer,Payal Sipahimalani,Tara Skelly,Karen Smith McCune,Nicholas D. Socci,Matthew G. Soloway,Anil K. Sood,Angela Tam,Donghui Tan,Roy Tarnuzzer,Nina Thiessen,R. Houston Thompson,Leigh B. Thorne,M. Tsao,Christopher B. Umbricht,David Van Den Berg,Erwin G. Van Meir,Umadevi Veluvolu,Douglas Voet,Linghua Wang,Paul Weinberger,Daniel J. Weisenberger,Dennis A. Wigle,Matthew D. Wilkerson,Richard K. Wilson,Boris Winterhoff,Maciej Wiznerowicz,Tina Wong,Wing Hing Wong,Liu Xi,Christina Yau,Hailei Zhang,Hongxin Zhang,Jiashan Zhang +1332 more