Open AccessIntegrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types
Author(s) -
Zhongqi Ge,
Jake Leighton,
Yumeng Wang,
Xinxin Peng,
Zhongyuan Chen,
Hu Chen,
Yutong Sun,
Fan Yao,
Jun Li,
Huiwen Zhang,
Jianfang Liu,
Craig D. Shriver,
Hai Hu,
Helen PiwnicaWorms,
Li Ma,
Han Liang,
Rory Johnson,
John A. Demchok,
Ina Felau,
Melpomeni Kasapi,
Martin L. Ferguson,
Carolyn M. Hutter,
Heidi J. Sofia,
Roy Tarnuzzer,
Zhining 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,
Sheila M. Reynolds,
Ilya Shmulevich,
Vésteinn Thórsson,
Wei Zhang,
Rehan Akbani,
Bradley M. Broom,
Apurva M. Hegde,
Zhenlin Ju,
Rupa S. Kanchi,
Anil Korkut,
Shiyun Ling,
Wenbin Liu,
Yiling Lu,
Gordon B. Mills,
Kwok-Shing Ng,
Arvind Rao,
Michael 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 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,
Viktoriya Korchina,
Charles Lee,
Lora Lewis,
Wei Li,
Xiuping Liu,
Todd M. Morgan,
Donna Morton,
Donna M. Muzny,
Jireh Santibanez,
Margi Sheth,
Eve Shinbrot,
Linghua Wang,
Min Wang,
David A. Wheeler,
Xi Liu,
Fengmei Zhao,
Julian M. Hess,
Elizabeth L. Appelbaum,
Matthew H. Bailey,
Matthew G. Cordes,
Li Ding,
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 N. 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 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 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,
Marc-Henri Stern,
Feixiong Cheng,
Sabina Signoretti,
Andrew Berchuck,
Darell D. Bigner,
Eric Lipp,
Jeffrey S. 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 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,
Chen Chu,
J. C. Houck,
Pawadee Lohavanichbutr,
Arndt Hartmann,
Robert Stoehr,
Helge Täubert,
Sven Wach,
Bernd Wullich,
Witold Kycler,
Dawid Murawa,
Maciej Wiznerowicz,
Ki Wha 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 R. 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,
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Tushar Patel,
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Michael Rivera,
Lewis R. Roberts,
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Melissa Stanton,
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Michael Torbenson,
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Carmen Behrens,
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Gian Luca Grazi,
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Simone Chevalier,
Ginette McKercher,
Kıvanç Birsoy,
Gene H. Barnett,
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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,
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Mohamed H. AbdelRahman,
Dina Aziz,
Sue Bell,
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Joe Hilty,
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Lynn Schoenfield,
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Dirk Schadendorf,
Marta Couce,
Markus Graefen,
Hartwig Huland,
Guido Sauter,
Thorsten Schlomm,
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Pierre Tennstedt,
Oluwole Olabode,
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Ashley Fehrenbach,
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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,
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,
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.2018.03.047
Subject(s) - ubiquitin , deubiquitinating enzyme , biology , cancer , gene , mdm2 , computational biology , cancer research , downregulation and upregulation , genetics , pten , signal transduction , pi3k/akt/mtor pathway
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies.
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