Open AccessComprehensive Characterization of Cancer Driver Genes and Mutations
Author(s) -
Matthew H. Bailey,
Collin Tokheim,
Eduard PortaPardo,
Sohini Sengupta,
Denis Bertrand,
Amila Weerasinghe,
Antonio Colaprico,
Michael C. Wendl,
Jaegil Kim,
Brendan Reardon,
Patrick KwokShing Ng,
Kang Jin Jeong,
Song Cao,
Zixing Wang,
Galen F. Gao,
Qingsong Gao,
Fang Wang,
Eric Minwei Liu,
Loris Mularoni,
Carlota Rubio-Pérez,
Niranjan Nagarajan,
Isidro CortésCiriano,
Daniel Cui Zhou,
Wen-Wei Liang,
Julian M. Hess,
Venkata Yellapantula,
David Tamborero,
Abel González-Pérez,
Chayaporn Suphavilai,
Jia Yu Ko,
Ekta Khurana,
Peter J. Park,
Eliezer M. Van Allen,
Han Liang,
Michael S. Lawrence,
Adam Godzik,
Núria López-Bigas,
Joshua M. Stuart,
David A. Wheeler,
Gad Getz,
Ken Chen,
Alexander J. Lazar,
Gordon B. Mills,
Rachel Karchin,
Li Ding,
Rory Johnson,
John A. Demchok,
Ina Felau,
Melpomeni Kasapi,
Martin L. Ferguson,
Carolyn M. Hutter,
Heidi J. Sofia,
Roy Tarnuzzer,
Linghua Wang,
Liming Yang,
Jean C. Zenklusen,
Jiashan Zhang,
Sudha Chudamani,
Jia Liu,
Laxmi Lolla,
Rashi Naresh,
Todd Pihl,
Qiang Sun,
Yunhu Wan,
Ye Wu,
Juok Cho,
Timothy Defreitas,
Scott Frazer,
Nils Gehlenborg,
David I. Heiman,
Pei Lin,
Thomas J. Giordano,
Michael S. Noble,
Gordon Saksena,
Doug Voet,
Hailei Zhang,
Brady Bernard,
Nyasha Chambwe,
Varsha Dhankani,
Theo Knijnenburg,
Roger Kramer,
Kalle Lein,
Yuexin Liu,
Michael Miller,
Sheila M. Reynolds,
Ilya Shmulevich,
Vésteinn Thórsson,
Wei Zhang,
Rehan Akbani,
Bradley M. Broom,
Apurva M. Hegde,
Zhenlin Ju,
Rupa S. Kanchi,
Anil Korkut,
Jun Li,
Shiyun Ling,
Wenbin Liu,
Yiling Lu,
Kwok-Shing Ng,
Arvind Rao,
Michael P. Ryan,
Jing Wang,
John N. Weinstein,
Jiexin Zhang,
Adam Abeshouse,
Joshua Armenia,
Debyani Chakravarty,
Walid K. Chatila,
Ino de Bruijn,
Benjamin E. Gross,
Zachary Heins,
Ritika Kundra,
Konnor La,
Marc Ladanyi,
Augustin Luna,
Moriah G. Nissan,
Angelica Ochoa,
Sarah Phillips,
Ed Reznik,
Francisco Sánchez-Vega,
Chris Sander,
Nikolaus Schultz,
Robert E. Sheridan,
S. Onur Sumer,
Yichao Sun,
Barry S. Taylor,
Jioajiao Wang,
Hongxin Zhang,
Pavana Anur,
Myron Peto,
Paul T. Spellman,
Christopher C. Benz,
Christopher K. Wong,
Christina Yau,
D. Neil Hayes,
Joel S. Parker,
Matthew D. Wilkerson,
Adrian Ally,
Miruna Balasundaram,
Reanne Bowlby,
Denise Brooks,
Rebecca Carlsen,
Eric Chuah,
Noreen Dhalla,
Robert A. Holt,
Steven J.M. Jones,
L. Sylvia,
Darlene Lee,
Yussanne Ma,
Marco A. Marra,
Michael Mayo,
Richard A. Moore,
Andrew J. Mungall,
Karen Mungall,
A. Gordon Robertson,
Sara Sadeghi,
Jacqueline E. Schein,
Payal Sipahimalani,
Angela Tam,
Nina Thiessen,
Kane Tse,
Tina Wong,
Ashton C. Berger,
Rameen Beroukhim,
Andrew D. Cherniack,
Carrie Cibulskis,
Stacey Gabriel,
Gavin Ha,
Matthew Meyerson,
Steven E. Schumacher,
Juliann Shih,
Melanie H. Kucherlapati,
Raju Kucherlapati,
Stephen B. Baylin,
Leslie Cope,
Ludmila Danilova,
Arnoud Boot,
Phillip H. Lai,
Dennis T. Maglinte,
David Van Den Berg,
Daniel J. Weisenberger,
J. Todd Auman,
Saianand Balu,
Tom Bodenheimer,
Huihui Fan,
Katherine A. Hoadley,
Alan P. Hoyle,
Corbin D. Jones,
Shaowu Meng,
Piotr A. Mieczkowski,
Lisle E. Mose,
Amy H. Perou,
Charles M. Perou,
Jeffrey Roach,
Yan Shi,
Janae V. Simons,
Tara Skelly,
Matthew G. Soloway,
Donghui Tan,
Umadevi Veluvolu,
Toshinori Hinoue,
Peter W. Laird,
Hui Shen,
Wanding Zhou,
Michelle Bellair,
Kyle Chang,
Kyle R. Covington,
Chad J. Creighton,
Huyen Dinh,
HarshaVardhan Doddapaneni,
Lawrence A. Donehower,
Jennifer Drummond,
Richard A. Gibbs,
Robert Glenn,
Walker Hale,
Yi Han,
Hai Hu,
Viktoriya Korchina,
Charles Lee,
Lora Lewis,
Wei Li,
Xiuping Liu,
Margaret Morgan,
Donna Morton,
Donna M. Muzny,
Jireh Santibanez,
Margi Sheth,
Eve Shinbrot,
Min Wang,
Liu Xi,
Fengmei Zhao,
Elizabeth L. Appelbaum,
Matthew G. Cordes,
Catrina C. Fronick,
Lucinda A. Fulton,
Robert S. Fulton,
Cyriac Kandoth,
Elaine R. Mardis,
Michael D. McLellan,
Christopher A. Miller,
Heather K. Schmidt,
Richard K. Wilson,
Daniel Crain,
Erin Curley,
Johanna Gardner,
Kevin Lau,
David Mallery,
Scott Morris,
Joseph Paulauskis,
Robert Penny,
Candace Shelton,
Troy Shelton,
Mark E. Sherman,
Eric Thompson,
Peggy Yena,
Jay Bowen,
Julie M. GastierFoster,
Mark Gerken,
Kristen M. Leraas,
Tara M. Lichtenberg,
Nilsa C. Ramirez,
Lisa Wise,
Erik Zmuda,
Niall M. Corcoran,
Tony Costello,
Christopher M. Hovens,
André Lopes Carvalho,
Ana Carolina de Carvalho,
José Humberto Tavares Guerreiro Fregnani,
Adhemar LongattoFilho,
Rui Manuel Reis,
Cristovam ScapulatempoNeto,
Henrique C.S. Silveira,
Daniel Onofre Vidal,
Andrew Burnette,
Jennifer Eschbacher,
Beth Hermes,
Ardene Noss,
Rosy Singh,
Matthew L. Anderson,
Patricia D. Castro,
Michael Ittmann,
David G. Huntsman,
Bernard Kohl,
Xuan Le,
Richard Thorp,
Chris Andry,
Elizabeth R. Duffy,
Vladimir Lyadov,
Oxana Paklina,
Galiya Setdikova,
Shabunin Av,
Mikhail Tavobilov,
Christopher McPherson,
Ronald E. Warnick,
Ross S. Berkowitz,
Daniel Cramer,
Colleen M. Feltmate,
Neil S. Horowitz,
Adam S. Kibel,
Michael G. Muto,
Chandrajit P. Raut,
Andrei Malykh,
Jill S. BarnholtzSloan,
Wendi Barrett,
Karen Devine,
Jordonna Fulop,
Quinn T. Ostrom,
Kristen Shimmel,
Yingli Wolinsky,
Andrew E. Sloan,
Agostino Maria De Rose,
Felice Giuliante,
Marc T. Goodman,
Beth Y. Karlan,
Curt H. Hagedorn,
John Eckman,
Jodi Harr,
Jerome Myers,
Kelinda Tucker,
Leigh Anne Zach,
Brenda Deyarmin,
Leonid Kvecher,
Caroline Larson,
Richard Mural,
Stella Somiari,
Aleš Vícha,
Tomáš Zelinka,
Joseph Bennett,
Mary Iacocca,
Brenda Rabeno,
Patricia Swanson,
Mathieu Latour,
Louis Lacombe,
Bernard Têtu,
Alain Bergeron,
Mary McGraw,
Susan M. Staugaitis,
John A. Chabot,
Hanina Hibshoosh,
Antonia R. Sepulveda,
Tao Su,
Timothy C. Wang,
Olga Potapova,
Olga Voronina,
Laurence Desjardins,
Odette Mariani,
Sergio Román-Román,
Xavier Sastre,
MarcHenri Stern,
Feixiong Cheng,
Sabina Signoretti,
Andrew Berchuck,
Darell D. Bigner,
Eric Lipp,
Jeffrey R. Marks,
Shan J. McCall,
Roger E. McLendon,
Angeles Alvarez Secord,
Alexis Sharp,
Madhusmita Behera,
Daniel J. Brat,
Amy Chen,
Keith A. Delman,
Seth Force,
Fadlo R. Khuri,
Kelly R. Magliocca,
Shishir K. Maithel,
Jeffrey J. Olson,
Taofeek K. Owonikoko,
Alan Pickens,
Suresh S. Ramalingam,
Dong Min Shin,
Gabriel Sica,
Erwin G. Van Meir,
Hongzheng Zhang,
Wil Eijckenboom,
Ad Gillis,
Esther Korpershoek,
Leendert H. J. Looijenga,
Wolter Oosterhuis,
Hans Stoop,
Kim E. van Kessel,
Ellen C. Zwarthoff,
Chiara Calatozzolo,
Lucia Cuppini,
Stefania Cuzzubbo,
Francesco DiMeco,
Gaetano Finocchiaro,
Luca Mattei,
Alessandro Perin,
Bianca Pollo,
Chu Chen,
J. C. Houck,
Pawadee Lohavanichbutr,
Arndt Hartmann,
Robert Stoehr,
Helge Täubert,
Sven Wach,
Bernd Wullich,
Witold Kycler,
Dawid Murawa,
Maciej Wiznerowicz,
Ki Wung Chung,
W. Jeffrey Edenfield,
Julie Martin,
Éric Baudin,
Glenn J. Bubley,
Raphael Bueno,
Assunta De Rienzo,
William G. Richards,
Steven N. Kalkanis,
Tom Mikkelsen,
Houtan Noushmehr,
Lisa Scarpace,
Nicolas Girard,
Marta Aymerich,
Elı́as Campo,
Eva Giné,
Armando López Guillermo,
Nguyen Van Bang,
Phan Thi Hanh,
Bùi Đức Phú,
Yufang Tang,
Howard Colman,
Kimberley Evason,
Peter Dottino,
John A. Martignetti,
Hani Gabra,
Hartmut Juhl,
Teniola Akeredolu,
Serghei Stepa,
Dave S.�B. Hoon,
Keunsoo Ahn,
Koo Jeong Kang,
Felix Beuschlein,
Anne Breggia,
Michael Birrer,
Debra Bell,
Mitesh J. Borad,
Alan H. Bryce,
Erik P. Castle,
Vishal S. Chandan,
John C. Cheville,
John A. Copland,
Michael B. Farnell,
Thomas J. Flotte,
Nasra H. Giama,
Thai H. Ho,
Michael L. Kendrick,
JeanPierre Kocher,
Karla Kopp,
Catherine D. Moser,
David M. Nagorney,
Daniel J. O’Brien,
Brian Patrick O’Neill,
Tushar Patel,
Gloria M. Petersen,
Florencia G. Que,
Michael Rivera,
Lewis R. Roberts,
Robert C. Smallridge,
Thomas C. Smyrk,
Melissa Stanton,
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Michael Torbenson,
Ju Yang,
Lizhi Zhang,
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Jaffer A. Ajani,
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Carmen Behrens,
Jolanta Bondaruk,
Russell Broaddus,
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Junya Fujimoto,
Charles C. Guo,
Christopher J. Logothetis,
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César A. Moran,
Lois M. Ramondetta,
David C. Rice,
Anil K. Sood,
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Timothy Thompson,
Patricia Troncoso,
Anne S. Tsao,
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Candace Carter,
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Peter Hersey,
Valerie Jakrot,
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Richard Kefford,
Kenneth Lee,
Georgina V. Long,
Graham J. Mann,
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Richard A. Scolyer,
Kerwin F. Shan,
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Jeremy Parfitt,
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Carlo Bifulco,
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Ronald R. de Krijger,
AnnePaule GimenezRoqueplo,
Alain Piché,
Simone Chevalier,
Ginette McKercher,
Kıvanç Birsoy,
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Cathy Brewer,
Carol Farver,
Theresa Naska,
Nathan A. Pennell,
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Cathy Schilero,
Kathy Smolenski,
Cecilia Williams,
Quaid Morris,
Jeffrey A. Borgia,
Mark Pool,
Christopher W. Seder,
Kerstin Junker,
Larsson Omberg,
Mikhail Dinkin,
George Manikhas,
Domenico Alvaro,
Maria Consiglia Bragazzi,
Vincenzo Cardinale,
Guido Carpino,
Eugenio Gaudio,
David Chesla,
Sandra Cottingham,
Michael Dubina,
Fedor Moiseenko,
Renumathy Dhanasekaran,
KarlFriedrich Becker,
Klaus–Peter Janssen,
Julia SlottaHuspenina,
Mohamed H. AbdelRahman,
Dina Aziz,
Sue Bell,
Colleen M. Cebulla,
Amy Davis,
Rebecca Duell,
J. Bradley Elder,
Joe Hilty,
Bahavna Kumar,
James C. Lang,
Norman L. Lehman,
Randy Mandt,
Phuong Nguyen,
Robert Pilarski,
Karan Rai,
Lynn Schoenfield,
Kelly Senecal,
Paul E. Wakely,
Paul Hansen,
Ronald M. Lechan,
James F. Powers,
Arthur S. Tischler,
William E. Grizzle,
Katherine C. Sexton,
Alison Kastl,
Joel Henderson,
Sima P. Porten,
Jens Waldmann,
Martin Faßnacht,
Dirk Schadendorf,
Marta Couce,
Markus Graefen,
Hartwig Huland,
Guido Sauter,
Thorsten Schlomm,
Ronald Simon,
Pierre Tennstedt,
Oluwole Olabode,
Mark A. Nelson,
Oliver F. Bathe,
Peter R. Carroll,
June M. Chan,
Philip J. DiSaia,
Pat Glenn,
Robin Kate Kelley,
Charles N. Landen,
Joanna Phillips,
Michael Prados,
Jeffry Simko,
Karen SmithMcCune,
Scott R. VandenBerg,
Kevin K. Roggin,
Ashley Fehrenbach,
Ady Kendler,
Suzanne Sifri,
Ruth Steele,
Antonio Jimeno,
Francis A. Carey,
Ian Forgie,
Massimo Mannelli,
Michael E. Carney,
Brenda Hernandez,
Benito Campos,
Christel HeroldMende,
Christin Jungk,
Andreas Unterberg,
Andreas von Deimling,
Aaron Bossler,
Joseph Galbraith,
Laura Jacobus,
Michael Knudson,
Tina Knutson,
Deqin Ma,
Mohammed Milhem,
Rita Sigmund,
Andrew K. Godwin,
Rashna Madan,
Howard G. Rosenthal,
Clement Adebamowo,
Sally N. Adebamowo,
Alex Boussioutas,
David G. Beer,
AnneMarie MesMasson,
Fred Saad,
Thèrése Bocklage,
Lisa M. Landrum,
Robert S. Mannel,
Kathleen Moore,
Katherine Moxley,
Russel Postier,
Joan L. Walker,
Rosemary E. Zuna,
Michaël Feldman,
Federico Valdivieso,
Rajiv Dhir,
James D. Luketich,
Edna M. Mora Pinero,
Mario Quintero-Aguilo,
Carlos Gilberto Carlotti,
José Sebastião dos Santos,
Rafael Kemp,
Ajith Sankarankuty,
Daniela Pretti da Cunha Tirapelli,
James W.F. Catto,
Kathy Agnew,
Elizabeth M. Swisher,
Jenette Creaney,
Bruce Robinson,
Carl Simon Shelley,
Eryn M. Godwin,
Sara Kendall,
Cassaundra Shipman,
Carol R. Bradford,
Thomas E. Carey,
Robert I. Haddad,
Jeffey Moyer,
Lisa A. Peterson,
Mark E. Prince,
Laura S. Rozek,
Gregory T. Wolf,
Rayleen Bowman,
Kwun M. Fong,
Ian A. Yang,
Robert J. Korst,
W. Kimryn Rathmell,
J. Leigh Fantacone-Campbell,
Jeffrey A. Hooke,
Albert J. Kovatich,
Craig D. Shriver,
John F. DiPersio,
Bettina F. Drake,
Ramaswamy Govindan,
Sharon E. Heath,
Timothy J. Ley,
Brian A. Van Tine,
Peter Westervelt,
Mark A. Rubin,
Jung Il Lee,
Natália D. Aredes,
Armaz Mariamidze
Publication year - 2018
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2018.02.060
Subject(s) - biology , gene , genetics , cancer , computational biology , mutation
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors.
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