Open AccessDriver Fusions and Their Implications in the Development and Treatment of Human Cancers
Author(s) -
Qingsong Gao,
Wen-Wei Liang,
Steven M. Foltz,
Gnanavel Mutharasu,
Reyka G. Jayasinghe,
Song Cao,
WenWei Liao,
Sheila M. Reynolds,
Matthew A. Wyczalkowski,
Lijun Yao,
Lihua Yu,
Sam Q. Sun,
Ken Chen,
Alexander J. Lazar,
Ryan C. Fields,
Michael C. Wendl,
Brian Andrew Van Tine,
Ravi Vij,
Feng Chen,
Matti Nykter,
Ilya Shmulevich,
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,
Gad Getz,
David I. Heiman,
Seungchan Kim,
Michael S. Lawrence,
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,
Vésteinn Thórsson,
Wei Zhang,
Rehan Akbani,
Bradley M. Broom,
Apurva M. Hegde,
Zhenlin Ju,
Rupa S. Kanchi,
Anil Korkut,
Jun Li,
Han Liang,
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,
Joshua Armenia,
Debyani Chakravarty,
Walid K. Chatila,
Ino de Bruijn,
Galen F. Gao,
Benjamin 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 P. Sheridan,
S. Onur Sumer,
Yichao Sun,
Barry S. Taylor,
Jioajiao Wang,
Hongxin Zhang,
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,
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 N. 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,
Todd M. Morgan,
Donna Morton,
Donna M. Muzny,
Jireh Santibanez,
Margi Sheth,
Eve Shinbrot,
Min Wang,
David A. Wheeler,
Xi Liu,
Fengmei Zhao,
Julian M. Hess,
Elizabeth L. Appelbaum,
Matthew H. Bailey,
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 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 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 K. Myers,
Kelinda Tucker,
Leigh Anne Zach,
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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,
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Odette Mariani,
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Xavier Sastre,
MarcHenri Stern,
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Darell D. Bigner,
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Shan J. McCall,
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Daniel J. Brat,
Amy Chen,
Keith A. Delman,
Seth Force,
Fadlo R. Khuri,
Kelly R. Magliocca,
Shishir K. Maithel,
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Taofeek K. Owonikoko,
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Suresh Ramalingam,
Dong Min Shin,
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Kim E. van Kessel,
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Francesco DiMeco,
Gaetano Finocchiaro,
Luca Mattei,
Alessandro Perin,
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June M. Chan,
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Karen SmithMcCune,
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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 N. 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,
B. W. 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 reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.03.050
Subject(s) - cancer research , biology , medicine , computational biology
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.
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