Divergent mutational processes distinguish hypoxic and normoxic tumours
Authors: Bhandari Vinayak , Li Constance H. , Bristow Robert G. , Boutros Paul C. ,   PCAWG Consortium, Aaltonen Lauri A. , Abascal Federico , Abeshouse Adam , Aburatani Hiroyuki , Adams David J. , Agrawal Nishant , Ahn Keun Soo , Ahn Sung-Min , Aikata Hiroshi , Akbani Rehan , Akdemir Kadir C. , Al-Ahmadie Hikmat , Al-Sedairy Sultan T. , Al-Shahrour Fatima , Alawi Malik , Albert Monique , Aldape Kenneth , Alexandrov Ludmil B. , Ally Adrian , Alsop Kathryn , Alvarez Eva G. , Amary Fernanda , Amin Samirkumar B. , Aminou Brice , Ammerpohl Ole , Anderson Matthew J. , Ang Yeng , Antonello Davide , Anur Pavana , Aparicio Samuel , Appelbaum Elizabeth L. , Arai Yasuhito , Aretz Axel , Arihiro Koji , Ariizumi Shun-ichi , Armenia Joshua , Arnould Laurent , Asa Sylvia , Assenov Yassen , Atwal Gurnit , Aukema Sietse , Auman J. Todd , Aure Miriam R. R. , Awadalla Philip , Aymerich Marta , Bader Gary D. , Baez-Ortega Adrian , Bailey Matthew H. , Bailey Peter J. , Balasundaram Miruna , Balu Saianand , Bandopadhayay Pratiti , Banks Rosamonde E. , Barbi Stefano , Barbour Andrew P. , Barenboim Jonathan , Barnholtz-Sloan Jill , Barr Hugh , Barrera Elisabet , Bartlett John , Bartolome Javier , Bassi Claudio , Bathe Oliver F. , Baumhoer Daniel , Bavi Prashant , Baylin Stephen B. , Bazant Wojciech , Beardsmore Duncan , Beck Timothy A. , Behjati Sam , Behren Andreas , Niu Beifang , Bell Cindy , Beltran Sergi , Benz Christopher , Berchuck Andrew , Bergmann Anke K. , Bergstrom Erik N. , Berman Benjamin P. , Berney Daniel M. , Bernhart Stephan H. , Beroukhim Rameen , Berrios Mario , Bersani Samantha , Bertl Johanna , Betancourt Miguel , Bhandari Vinayak , Bhosle Shriram G. , Biankin Andrew V. , Bieg Matthias , Bigner Darell , Binder Hans , Birney Ewan , Birrer Michael , Biswas Nidhan K. , Bjerkehagen Bodil , Bodenheimer Tom , Boice Lori , Bonizzato Giada , De Bono Johann S. , Boot Arnoud , Bootwalla Moiz S. , Borg Ake , Borkhardt Arndt , Boroevich Keith A. , Borozan Ivan , Borst Christoph , Bosenberg Marcus , Bosio Mattia , Boultwood Jacqueline , Bourque Guillaume , Boutros Paul C. , Bova G. Steven , Bowen David T. , Bowlby Reanne , Bowtell David D. L. , Boyault Sandrine , Boyce Rich , Boyd Jeffrey , Brazma Alvis , Brennan Paul , Brewer Daniel S. , Brinkman Arie B. , Bristow Robert G. , Broaddus Russell R. , Brock Jane E. , Brock Malcolm , Broeks Annegien , Brooks Angela N. , Brooks Denise , Brors Benedikt , Brunak Søren , Bruxner Timothy J. C. , Bruzos Alicia L. , Buchanan Alex , Buchhalter Ivo , Buchholz Christiane , Bullman Susan , Burke Hazel , Burkhardt Birgit , Burns Kathleen H. , Busanovich John , Bustamante Carlos D. , Butler Adam P. , Butte Atul J. , Byrne Niall J. , Børresen-Dale Anne-Lise , Caesar-Johnson Samantha J. , Cafferkey Andy , Cahill Declan , Calabrese Claudia , Caldas Carlos , Calvo Fabien , Camacho Niedzica , Campbell Peter J. , Campo Elias , Cantù Cinzia , Cao Shaolong , Carey Thomas E. , Carlevaro-Fita Joana , Carlsen Rebecca , Cataldo Ivana , Cazzola Mario , Cebon Jonathan , Cerfolio Robert , Chadwick Dianne E. , Chakravarty Dimple , Chalmers Don , Chan Calvin Wing Yiu , Chan Kin , Chan-Seng-Yue Michelle , Chandan Vishal S. , Chang David K. , Chanock Stephen J. , Chantrill Lorraine A. , Chateigner Aurélien , Chatterjee Nilanjan , Chayama Kazuaki , Chen Hsiao-Wei , Chen Jieming , Chen Ken , Chen Yiwen , Chen Zhaohong , Cherniack Andrew D. , Chien Jeremy , Chiew Yoke-Eng , Chin Suet-Feung , Cho Juok , Cho Sunghoon , Choi Jung Kyoon , Choi Wan , Chomienne Christine , Chong Zechen , Choo Su Pin , Chou Angela , Christ Angelika N. , Christie Elizabeth L. , Chuah Eric , Cibulskis Carrie , Cibulskis Kristian , Cingarlini Sara , Clapham Peter , Claviez Alexander , Cleary Sean , Cloonan Nicole , Cmero Marek , Collins Colin C. , Connor Ashton A. , Cooke Susanna L. , Cooper Colin S. , Cope Leslie , Corbo Vincenzo , Cordes Matthew G. , Cordner Stephen M. , Cortés-Ciriano Isidro , Covington Kyle , Cowin Prue A. , Craft Brian , Craft David , Creighton Chad J. , Cun Yupeng , Curley Erin , Cutcutache Ioana , Czajka Karolina , Czerniak Bogdan , Dagg Rebecca A. , Danilova Ludmila , Davi Maria Vittoria , Davidson Natalie R. , Davies Helen , Davis Ian J. , Davis-Dusenbery Brandi N. , Dawson Kevin J. , De La Vega Francisco M. , De Paoli-Iseppi Ricardo , Defreitas Timothy , Tos Angelo P. Dei , Delaneau Olivier , Demchok John A. , Demeulemeester Jonas , Demidov German M. , Demircioğlu Deniz , Dennis Nening M. , Denroche Robert E. , Dentro Stefan C. , Desai Nikita , Deshpande Vikram , Deshwar Amit G. , Desmedt Christine , Deu-Pons Jordi , Dhalla Noreen , Dhani Neesha C. , Dhingra Priyanka , Dhir Rajiv , DiBiase Anthony , Diamanti Klev , Ding Li , Ding Shuai , Dinh Huy Q. , Dirix Luc , Doddapaneni HarshaVardhan , Donmez Nilgun , Dow Michelle T. , Drapkin Ronny , Drechsel Oliver , Drews Ruben M. , Serge Serge , Dudderidge Tim , Dueso-Barroso Ana , Dunford Andrew J. , Dunn Michael , Dursi Lewis Jonathan , Duthie Fraser R. , Dutton-Regester Ken , Eagles Jenna , Easton Douglas F. , Edmonds Stuart , Edwards Paul A. , Edwards Sandra E. , Eeles Rosalind A. , Ehinger Anna , Eils Juergen , Eils Roland , El-Naggar Adel , Eldridge Matthew , Ellrott Kyle , Erkek Serap , Escaramis Georgia , Espiritu Shadrielle M. G. , Estivill Xavier , Etemadmoghadam Dariush , Eyfjord Jorunn E. , Faltas Bishoy M. , Fan Daiming , Fan Yu , Faquin William C. , Farcas Claudiu , Fassan Matteo , Fatima Aquila , Favero Francesco , Fayzullaev Nodirjon , Felau Ina , Fereday Sian , Ferguson Martin L. , Ferretti Vincent , Feuerbach Lars , Field Matthew A. , Fink J. Lynn , Finocchiaro Gaetano , Fisher Cyril , Fittall Matthew W. , Fitzgerald Anna , Fitzgerald Rebecca C. , Flanagan Adrienne M. , Fleshner Neil E. , Flicek Paul , Foekens John A. , Fong Kwun M. , Fonseca Nuno A. , Foster Christopher S. , Fox Natalie S. , Fraser Michael , Frazer Scott , Frenkel-Morgenstern Milana , Friedman William , Frigola Joan , Fronick Catrina C. , Fujimoto Akihiro , Fujita Masashi , Fukayama Masashi , Fulton Lucinda A. , Fulton Robert S. , Furuta Mayuko , Futreal P. Andrew , Füllgrabe Anja , Gabriel Stacey B. , Gallinger Steven , Gambacorti-Passerini Carlo , Gao Jianjiong , Gao Shengjie , Garraway Levi , Garred Øystein , Garrison Erik , Garsed Dale W. , Gehlenborg Nils , Gelpi Josep L. L. , George Joshy , Gerhard Daniela S. , Gerhauser Clarissa , Gershenwald Jeffrey E. , Gerstein Mark , Gerstung Moritz , Getz Gad , Ghori Mohammed , Ghossein Ronald , Giama Nasra H. , Gibbs Richard A. , Gibson Bob , Gill Anthony J. , Gill Pelvender , Giri Dilip D. , Glodzik Dominik , Gnanapragasam Vincent J. , Goebler Maria Elisabeth , Goldman Mary J. , Gomez Carmen , Gonzalez Santiago , Gonzalez-Perez Abel , Gordenin Dmitry A. , Gossage James , Gotoh Kunihito , Govindan Ramaswamy , Grabau Dorthe , Graham Janet S. , Grant Robert C. , Green Anthony R. , Green Eric , Greger Liliana , Grehan Nicola , Grimaldi Sonia , Grimmond Sean M. , Grossman Robert L. , Grundhoff Adam , Gundem Gunes , Guo Qianyun , Gupta Manaswi , Gupta Shailja , Gut Ivo G. , Gut Marta , Göke Jonathan , Ha Gavin , Haake Andrea , Haan David , Haas Siegfried , Haase Kerstin , Haber James E. , Habermann Nina , Hach Faraz , Haider Syed , Hama Natsuko , Hamdy Freddie C. , Hamilton Anne , Hamilton Mark P. , Han Leng , Hanna George B. , Hansmann Martin , Haradhvala Nicholas J. , Harismendy Olivier , Harliwong Ivon , Harmanci Arif O. , Harrington Eoghan , Hasegawa Takanori , Haussler David , Hawkins Steve , Hayami Shinya , Hayashi Shuto , Hayes D. Neil , Hayes Stephen J. , Hayward Nicholas K. , Hazell Steven , He Yao , Heath Allison P. , Heath Simon C. , Hedley David , Hegde Apurva M. , Heiman David I. , Heinold Michael C. , Heins Zachary , Heisler Lawrence E. , Hellstrom-Lindberg Eva , Helmy Mohamed , Heo Seong Gu , Hepperla Austin J. , Heredia-Genestar José María , Herrmann Carl , Hersey Peter , Hess Julian M. , Hilmarsdottir Holmfridur , Hinton Jonathan , Hirano Satoshi , Hiraoka Nobuyoshi , Hoadley Katherine A. , Hobolth Asger , Hodzic Ermin , Hoell Jessica I. , Hoffmann Steve , Hofmann Oliver , Holbrook Andrea , Holik Aliaksei Z. , Hollingsworth Michael A. , Holmes Oliver , Holt Robert A. , Hong Chen , Hong Eun Pyo , Hong Jongwhi H. , Hooijer Gerrit K. , Hornshøj Henrik , Hosoda Fumie , Hou Yong , Hovestadt Volker , Howat William , Hoyle Alan P. , Hruban Ralph H. , Hu Jianhong , Hu Taobo , Hua Xing , Huang Kuan-lin , Huang Mei , Huang Mi Ni , Huang Vincent , Huang Yi , Huber Wolfgang , Hudson Thomas J. , Hummel Michael , Hung Jillian A. , Huntsman David , Hupp Ted R. , Huse Jason , Huska Matthew R. , Hutter Barbara , Hutter Carolyn M. , Hübschmann Daniel , Iacobuzio-Donahue Christine A. , Imbusch Charles David , Imielinski Marcin , Imoto Seiya , Isaacs William B. , Isaev Keren , Ishikawa Shumpei , Iskar Murat , Islam S. M. Ashiqul , Ittmann Michael , Ivkovic Sinisa , Izarzugaza Jose M. G. , Jacquemier Jocelyne , Jakrot Valerie , Jamieson Nigel B. , Jang Gun Ho , Jang Se Jin , Jayaseelan Joy C. , Jayasinghe Reyka , Jefferys Stuart R. , Jegalian Karine , Jennings Jennifer L. , Jeon Seung-Hyup , Jerman Lara , Ji Yuan , Jiao Wei , Johansson Peter A. , Johns Amber L. , Johns Jeremy , Johnson Rory , Johnson Todd A. , Jolly Clemency , Joly Yann , Jonasson Jon G. , Jones Corbin D. , Jones David R. , Jones David T. W. , Jones Nic , Jones Steven J. M. , Jonkers Jos , Ju Young Seok , Juhl Hartmut , Jung Jongsun , Juul Malene , Juul Randi Istrup , Juul Sissel , Jäger Natalie , Kabbe Rolf , Kahles Andre , Kahraman Abdullah , Kaiser Vera B. , Kakavand Hojabr , Kalimuthu Sangeetha , von Kalle Christof , Kang Koo Jeong , Karaszi Katalin , Karlan Beth , Karlić Rosa , Karsch Dennis , Kasaian Katayoon , Kassahn Karin S. , Katai Hitoshi , Kato Mamoru , Katoh Hiroto , Kawakami Yoshiiku , Kay Jonathan D. , Kazakoff Stephen H. , Kazanov Marat D. , Keays Maria , Kebebew Electron , Kefford Richard F. , Kellis Manolis , Kench James G. , Kennedy Catherine J. , Kerssemakers Jules N. A. , Khoo David , Khoo Vincent , Khuntikeo Narong , Khurana Ekta , Kilpinen Helena , Kim Hark Kyun , Kim Hyung-Lae , Kim Hyung-Yong , Kim Hyunghwan , Kim Jaegil , Kim Jihoon , Kim Jong K. , Kim Youngwook , King Tari A. , Klapper Wolfram , Kleinheinz Kortine , Klimczak Leszek J. , Knappskog Stian , Kneba Michael , Knoppers Bartha M. , Koh Youngil , Jan Komorowski  , Komura Daisuke , Komura Mitsuhiro , Kong Gu , Kool Marcel , Korbel Jan O. , Korchina Viktoriya , Korshunov Andrey , Koscher Michael , Koster Roelof , Kote-Jarai Zsofia , Koures Antonios , Kovacevic Milena , Kremeyer Barbara , Kretzmer Helene , Kreuz Markus , Krishnamurthy Savitri , Kube Dieter , Kumar Kiran , Kumar Pardeep , Kumar Sushant , Kumar Yogesh , Kundra Ritika , Kübler Kirsten , Küppers Ralf , Lagergren Jesper , Lai Phillip H. , Laird Peter W. , Lakhani Sunil R. , Lalansingh Christopher M. , Lalonde Emilie , Lamaze Fabien C. , Lambert Adam , Lander Eric , Landgraf Pablo , Landoni Luca , Langerød Anita , Lanzós Andrés , Larsimont Denis , Larsson Erik , Lathrop Mark , Lau Loretta M. S. , Lawerenz Chris , Lawlor Rita T. , Lawrence Michael S. , Lazar Alexander J. , Lazic Ana Mijalkovic , Le Xuan , Lee Darlene , Lee Donghoon , Lee Eunjung Alice , Lee Hee Jin , Lee Jake June-Koo , Lee Jeong-Yeon , Lee Juhee , Lee Ming Ta Michael , Lee-Six Henry , Lehmann Kjong-Van , Lehrach Hans , Lenze Dido , Leonard Conrad R. , Leongamornlert Daniel A. , Leshchiner Ignaty , Letourneau Louis , Letunic Ivica , Levine Douglas A. , Lewis Lora , Ley Tim , Li Chang , Li Constance H. , Li Haiyan Irene , Li Jun , Li Lin , Li Shantao , Li Siliang , Li Xiaobo , Li Xiaotong , Li Xinyue , Li Yilong , Liang Han , Liang Sheng-Ben , Lichter Peter , Lin Pei , Lin Ziao , Linehan W. M. , Lingjærde Ole Christian , Liu Dongbing , Liu Eric Minwei , Liu Fei-Fei Fei , Liu Fenglin , Liu Jia , Liu Xingmin , Livingstone Julie , Livitz Dimitri , Livni Naomi , Lochovsky Lucas , Loeffler Markus , Long Georgina V. , Lopez-Guillermo Armando , Lou Shaoke , Louis David N. , Lovat Laurence B. , Lu Yiling , Lu Yong-Jie , Lu Youyong , Luchini Claudio , Lungu Ilinca , Luo Xuemei , Luxton Hayley J. , Lynch Andy G. , Lype Lisa , López Cristina , López-Otín Carlos , Ma Eric Z. , Ma Yussanne , MacGrogan Gaetan , MacRae Shona , Macintyre Geoff , Madsen Tobias , Maejima Kazuhiro , Mafficini Andrea , Maglinte Dennis T. , Maitra Arindam , Majumder Partha P. , Malcovati Luca , Malikic Salem , Malleo Giuseppe , Mann Graham J. , Mantovani-Löffler Luisa , Marchal Kathleen , Marchegiani Giovanni , Mardis Elaine R. , Margolin Adam A. , Marin Maximillian G. , Markowetz Florian , Markowski Julia , Marks Jeffrey , Marques-Bonet Tomas , Marra Marco A. , Marsden Luke , Martens John W. M. , Martin Sancha , Martin-Subero Jose I. , Martincorena Iñigo , Martinez-Fundichely Alexander , Maruvka Yosef E. , Mashl R. Jay , Massie Charlie E. , Matthew Thomas J. , Matthews Lucy , Mayer Erik , Mayes Simon , Mayo Michael , Mbabaali Faridah , McCune Karen , McDermott Ultan , McGillivray Patrick D. , McLellan Michael D. , McPherson John D. , McPherson John R. , McPherson Treasa A. , Meier Samuel R. , Meng Alice , Meng Shaowu , Menzies Andrew , Merrett Neil D. , Merson Sue , Meyerson Matthew , Meyerson William , Mieczkowski Piotr A. , Mihaiescu George L. , Mijalkovic Sanja , Mikkelsen Tom , Milella Michele , Mileshkin Linda , Miller Christopher A. , Miller David K. , Miller Jessica K. , Mills Gordon B. , Milovanovic Ana , Minner Sarah , Miotto Marco , Arnau Gisela Mir , Mirabello Lisa , Mitchell Chris , Mitchell Thomas J. , Miyano Satoru , Miyoshi Naoki , Mizuno Shinichi , Molnár-Gábor Fruzsina , Moore Malcolm J. , Moore Richard A. , Morganella Sandro , Morris Quaid D. , Morrison Carl , Mose Lisle E. , Moser Catherine D. , Muiños Ferran , Mularoni Loris , Mungall Andrew J. , Mungall Karen , Musgrove Elizabeth A. , Mustonen Ville , Mutch David , Muyas Francesc , Muzny Donna M. , Muñoz Alfonso , Myers Jerome , Myklebost Ola , Möller Peter , Nagae Genta , Nagrial Adnan M. , Nahal-Bose Hardeep K. , Nakagama Hitoshi , Nakagawa Hidewaki , Nakamura Hiromi , Nakamura Toru , Nakano Kaoru , Nandi Tannistha , Nangalia Jyoti , Nastic Mia , Navarro Arcadi , Navarro Fabio C. P. , Neal David E. , Nettekoven Gerd , Newell Felicity , Newhouse Steven J. , Newton Yulia , Ng Alvin Wei Tian , Ng Anthony , Nicholson Jonathan , Nicol David , Nie Yongzhan , Nielsen G. Petur , Nielsen Morten Muhlig , Nik-Zainal Serena , Noble Michael S. , Nones Katia , Northcott Paul A. , Notta Faiyaz , O’Connor Brian D. , O’Donnell Peter , O’Donovan Maria , O’Meara Sarah , O’Neill Brian Patrick , O’Neill J. Robert , Ocana David , Ochoa Angelica , Oesper Layla , Ogden Christopher , Ohdan Hideki , Ohi Kazuhiro , Ohno-Machado Lucila , Oien Karin A. , Ojesina Akinyemi I. , Ojima Hidenori , Okusaka Takuji , Omberg Larsson , Ong Choon Kiat , Ossowski Stephan , Ott German , Ouellette B. F. Francis , P’ng Christine , Paczkowska Marta , Paiella Salvatore , Pairojkul Chawalit , Pajic Marina , Pan-Hammarström Qiang , Papaemmanuil Elli , Papatheodorou Irene , Paramasivam Nagarajan , Park Ji Wan , Park Joong-Won , Park Keunchil , Park Kiejung , Park Peter J. , Parker Joel S. , Parsons Simon L. , Pass Harvey , Pasternack Danielle , Pastore Alessandro , Patch Ann-Marie , Pauporté Iris , Pea Antonio , Pearson John V. , Pedamallu Chandra Sekhar , Pedersen Jakob Skou , Pederzoli Paolo , Peifer Martin , Pennell Nathan A. , Perou Charles M. , Perry Marc D. , Petersen Gloria M. , Peto Myron , Petrelli Nicholas , Petryszak Robert , Pfister Stefan M. , Phillips Mark , Pich Oriol , Pickett Hilda A. , Pihl Todd D. , Pillay Nischalan , Pinder Sarah , Pinese Mark , Pinho Andreia V. , Pitkänen Esa , Pivot Xavier , Piñeiro-Yáñez Elena , Planko Laura , Plass Christoph , Polak Paz , Pons Tirso , Popescu Irinel , Potapova Olga , Prasad Aparna , Preston Shaun R. , Prinz Manuel , Pritchard Antonia L. , Prokopec Stephenie D. , Provenzano Elena , Puente Xose S. , Puig Sonia , Puiggròs Montserrat , Pulido-Tamayo Sergio , Pupo Gulietta M. , Purdie Colin A. , Quinn Michael C. , Rabionet Raquel , Rader Janet S. , Radlwimmer Bernhard , Radovic Petar , Raeder Benjamin , Raine Keiran M. , Ramakrishna Manasa , Ramakrishnan Kamna , Ramalingam Suresh , Raphael Benjamin J. , Rathmell W. Kimryn , Rausch Tobias , Reifenberger Guido , Reimand Jüri , Reis-Filho Jorge , Reuter Victor , Reyes-Salazar Iker , Reyna Matthew A. , Reynolds Sheila M. , Rheinbay Esther , Riazalhosseini Yasser , Richardson Andrea L. , Richter Julia , Ringel Matthew , Ringnér Markus , Rino Yasushi , Rippe Karsten , Roach Jeffrey , Roberts Lewis R. , Roberts Nicola D. , Roberts Steven A. , Robertson A. Gordon , Robertson Alan J. , Rodriguez Javier Bartolomé , Rodriguez-Martin Bernardo , Rodríguez-González F. Germán , Roehrl Michael H. A. , Rohde Marius , Rokutan Hirofumi , Romieu Gilles , Rooman Ilse , Roques Tom , Rosebrock Daniel , Rosenberg Mara , Rosenstiel Philip C. , Rosenwald Andreas , Rowe Edward W. , Royo Romina , Rozen Steven G. , Rubanova Yulia , Rubin Mark A. , Rubio-Perez Carlota , Rudneva Vasilisa A. , Rusev Borislav C. , Ruzzenente Andrea , Rätsch Gunnar , Sabarinathan Radhakrishnan , Sabelnykova Veronica Y. , Sadeghi Sara , Sahinalp S. Cenk , Saini Natalie , Saito-Adachi Mihoko , Saksena Gordon , Salcedo Adriana , Salgado Roberto , Salichos Leonidas , Sallari Richard , Saller Charles , Salvia Roberto , Sam Michelle , Samra Jaswinder S. , Sanchez-Vega Francisco , Sander Chris , Sanders Grant , Sarin Rajiv , Sarrafi Iman , Sasaki-Oku Aya , Sauer Torill , Sauter Guido , Saw Robyn P. M. , Scardoni Maria , Scarlett Christopher J. , Scarpa Aldo , Scelo Ghislaine , Schadendorf Dirk , Schein Jacqueline E. , Schilhabel Markus B. , Schlesner Matthias , Schlomm Thorsten , Schmidt Heather K. , Schramm Sarah-Jane , Schreiber Stefan , Schultz Nikolaus , Schumacher Steven E. , Schwarz Roland F. , Scolyer Richard A. , Scott David , Scully Ralph , Seethala Raja , Segre Ayellet V. , Selander Iris , Semple Colin A. , Senbabaoglu Yasin , Sengupta Subhajit , Sereni Elisabetta , Serra Stefano , Sgroi Dennis C. , Shackleton Mark , Shah Nimish C. , Shahabi Sagedeh , Shang Catherine A. , Shang Ping , Shapira Ofer , Shelton Troy , Shen Ciyue , Shen Hui , Shepherd Rebecca , Shi Ruian , Shi Yan , Shiah Yu-Jia , Shibata Tatsuhiro , Shih Juliann , Shimizu Eigo , Shimizu Kiyo , Shin Seung Jun , Shiraishi Yuichi , Shmaya Tal , Shmulevich Ilya , Shorser Solomon I. , Short Charles , Shrestha Raunak , Shringarpure Suyash S. , Shriver Craig , Shuai Shimin , Sidiropoulos Nikos , Siebert Reiner , Sieuwerts Anieta M. , Sieverling Lina , Signoretti Sabina , Sikora Katarzyna O. , Simbolo Michele , Simon Ronald , Simons Janae V. , Simpson Jared T. , Simpson Peter T. , Singer Samuel , Sinnott-Armstrong Nasa , Sipahimalani Payal , Skelly Tara J. , Smid Marcel , Smith Jaclyn , Smith-McCune Karen , Socci Nicholas D. , Sofia Heidi J. , Soloway Matthew G. , Song Lei , Sood Anil K. , Sothi Sharmila , Sotiriou Christos , Soulette Cameron M. , Span Paul N. , Spellman Paul T. , Sperandio Nicola , Spillane Andrew J. , Spiro Oliver , Spring Jonathan , Staaf Johan , Stadler Peter F. , Staib Peter , Stark Stefan G. , Stebbings Lucy , Stefánsson Ólafur Andri , Stegle Oliver , Stein Lincoln D. , Stenhouse Alasdair , Stewart Chip , Stilgenbauer Stephan , Stobbe Miranda D. , Stratton Michael R. , Stretch Jonathan R. , Struck Adam J. , Stuart Joshua M. , Stunnenberg Henk G. , Su Hong , Su Xiaoping , Sun Ren X. , Sungalee Stephanie , Susak Hana , Suzuki Akihiro , Sweep Fred , Szczepanowski Monika , Sültmann Holger , Yugawa Takashi , Tam Angela , Tamborero David , Tan Benita Kiat Tee , Tan Donghui , Tan Patrick , Tanaka Hiroko , Taniguchi Hirokazu , Tanskanen Tomas J. , Tarabichi Maxime , Tarnuzzer Roy , Tarpey Patrick , Taschuk Morgan L. , Tatsuno Kenji , Tavaré Simon , Taylor Darrin F. , Taylor-Weiner Amaro , Teague Jon W. , Teh Bin Tean , Tembe Varsha , Temes Javier , Thai Kevin , Thayer Sarah P. , Thiessen Nina , Thomas Gilles , Thomas Sarah , Thompson Alan , Thompson Alastair M. , Thompson John F. 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M. , van de Vijver Marc J. , van’t Veer L. , von Mering Christian 
Published: February 2020

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations inTP53,MYCandPTENare enriched in hypoxic tumours, and mutations inPTENinteract with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.