Open AccessOncogenic Signaling Pathways in The Cancer Genome Atlas
Author(s) -
Francisco Sánchez-Vega,
Marco Mina,
Joshua Armenia,
Walid K. Chatila,
Augustin Luna,
Konnor La,
Sofia Dimitriadoy,
David L. Liu,
Havish S. Kantheti,
Sadegh Saghafinia,
Debyani Chakravarty,
Foysal Daian,
Qingsong Gao,
Matthew H. Bailey,
Wen-Wei Liang,
Steven M. Foltz,
Ilya Shmulevich,
Li Ding,
Zachary Heins,
Angelica Ochoa,
Benjamin Groß,
Galen F. Gao,
Hongxin Zhang,
Ritika Kundra,
Cyriac Kandoth,
Istemi Bahceci,
Leonard Dervishi,
Uḡur Doḡrusöz,
Wanding Zhou,
Hui Shen,
Peter W. Laird,
Gregory P. Way,
Casey S. Greene,
Han Liang,
Yonghong Xiao,
Chen Wang,
Antonio Iavarone,
Alice H. Berger,
Trever G. Bivona,
Alexander J. Lazar,
Gary D. Hammer,
Thomas J. Giordano,
Lawrence N. Kwong,
Grant A. McArthur,
Chenfei Huang,
Aaron D. Tward,
Mitchell J. Frederick,
Frank McCormick,
Matthew Meyerson,
Eliezer M. Van Allen,
Andrew D. Cherniack,
Giovanni Ciriello,
Chris Sander,
Nikolaus Schultz,
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,
Gad Getz,
David I. Heiman,
Seungchan Kim,
Michael S. Lawrence,
Pei Lin,
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,
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,
Gordon B. Mills,
Kwok-Shing Ng,
Arvind Rao,
Michael P. Ryan,
Jing Wang,
John N. Weinstein,
Jiexin Zhang,
Adam Abeshouse,
Ino de Bruijn,
Benjamin E. Gross,
Marc Ladanyi,
Moriah G. Nissan,
Sarah Phillips,
Ed Reznik,
Robert P. Sheridan,
S. Onur Sumer,
Yichao Sun,
Barry S. Taylor,
Jioajiao Wang,
Pavana Anur,
Myron Peto,
Paul T. Spellman,
Christopher C. Benz,
Joshua M. Stuart,
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,
Carrie Cibulskis,
Stacey Gabriel,
Gavin Ha,
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,
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,
David A. Wheeler,
Liu Xi,
Fengmei Zhao,
Julian M. Hess,
Elizabeth L. Appelbaum,
Matthew G. Cordes,
Catrina C. Fronick,
Lucinda A. Fulton,
Robert S. Fulton,
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 M. Thompson,
Peggy Yena,
Jay Bowen,
Julie M. Gastier-Foster,
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 W. 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 K. 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 M. 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,
Chen Chu,
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 J. 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 R. 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,
R. Houston Thompson,
Michael Torbenson,
Ju Dong Yang,
Lizhi Zhang,
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Jaffer A. Ajani,
Ana Maria Angulo Gonzalez,
Carmen Behrens,
Jolanta Bondaruk,
Russell Broaddus,
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Junya Fujimoto,
Charles C. Guo,
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César A. Moran,
Lois M. Ramondetta,
David Rice,
Anil K. Sood,
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Timothy Thompson,
Patricia Troncoso,
Anne S. Tsao,
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Kenneth Lee,
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Graham J. Mann,
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Robyn P.M. Saw,
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Kerwin F. Shan,
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Carlo Bifulco,
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Mirella Marino,
Roberta Merola,
Ronald R. de Krijger,
AnnePaule GimenezRoqueplo,
Alain Piché,
Simone Chevalier,
Ginette McKercher,
Kıvanç Birsoy,
Gene H. Barnett,
Cathy Brewer,
Carol Farver,
Theresa Naska,
Nathan A. Pennell,
Daniel P. Raymond,
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 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 D. 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 Walker,
Rosemary E. Zuna,
Michael D. 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.2018.03.035
Subject(s) - biology , genome , cancer , genetics , computational biology , atlas (anatomy) , signal transduction , cancer research , gene , paleontology
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.
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