Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types
2018
- 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
- Samantha J. Caesar-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 (Julia) 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
- Jaegil Kim
- Michael S. Lawrence
- Pei Lin
- Sam Meier
- Michael S. Noble
- Gordon Saksena
- Doug Voet
- Hailei Zhang
- Brady Bernard
- Nyasha Chambwe
- Varsha Dhankani
- Theo Knijnenburg
- Roger Kramer
- Kalle Leinonen
- Yuexin Liu
- Michael B. Miller
- Sheila Reynolds
- Ilya Shmulevich
- Vesteinn Thorsson
- Wei Zhang
- Rehan Akbani
- Bradley McIntosh Broom
- Apurva M. Hegde
- Zhenlin Ju
- Rupa S. Kanchi
- Anil Korkut
- Han Liang
- Shiyun Ling
- Wenbin Liu
- Yiling Lu
- Gordon B. Mills
- Kwok-Shing Ng
- Arvind Rao
- Michael T. Ryan
- Jing Wang
- John N. Weinstein
- Jiexin Zhang
- Adam Abeshouse
- Joshua Armenia
- Debyani Chakravarty
- Walid K. Chatila
- Ino de Bruijn
- Jianjiong Gao
- Benjamin E. Gross
- Zachary J. Heins
- Ritika Kundra
- Konnor La
- Marc Ladanyi
- Augustin Luna
- Moriah G. Nissan
- Angelica Ochoa
- Sarah M. Phillips
- Ed Reznik
- Francisco Sanchez-Vega
- Chris Sander
- Nikolaus Schultz
- Robert L. Sheridan
- S. Onur Sumer
- Yichao Sun
- Barry S. Taylor
- Jioajiao Wang
- Hongxin Zhang
- Pavana Anur
- Myron Peto
- Paul Spellman
- Christopher C. Benz
- Joshua M. Stuart
- Chris K.C. 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
- Katayoon Kasaian
- 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
- Galen F. Gao
- Gavin Ha
- Matthew Meyerson
- Steven E. Schumacher
- Juliann Shih
- Melanie H. Kucherlapati
- Raju Kucherlapati
- Stephen B. Baylin
- Leslie Cope
- Ludmila Danilova
- Moiz S. Bootwalla
- Phillip H. Lai
- Dennis T. Maglinte
- David Van Den Berg
- Daniel J. Weisenberger
- J. Todd Auman
- Saianand Balu
- Tom Bodenheimer
- Cheng Fan
- Katherine A. Hoadley
- Alan P. Hoyle
- Stuart R. Jefferys
- 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
- Huihui Fan
- 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
- Jianhong Hu
- Viktoriya Korchina
- Sandra J. Lee
- Lora Lewis
- Wei Li
- Xiuping Liu
- Margaret Morgan
- Donna Morton
- Donna M. Muzny
- Jireh Santibanez
- Margi Sheth
- Eve Shinbrot
- Linghua Wang
- Min Wang
- David A. Wheeler
- Liu Xi
- Fengmei Zhao
- Julian Hess
- Elizabeth L. Appelbaum
- Michael 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 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 Hovens
- André Carlos Ponce de Leon Ferreira de Carvalho
- Ana C. de Carvalho
- José Humberto Tavares Guerreiro Fregnani
- Adhemar Longatto-Filho
- Rui Manuel Reis
- Cristovam Scapulatempo-Neto
- Henrique Silveira
- Daniel O. 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
- Alexey Shabunin
- Mikhail Tavobilov
- Christopher McPherson
- Ronald E. Warnick
- Ross S. Berkowitz
- Daniel W. Cramer
- Colleen Feltmate
- Neil S. Horowitz
- Adam S. Kibel
- Michael G. Muto
- Chandrajit P. Raut
- Andrei Malykh
- Jill S. Barnholtz Sloan
- Wendi Barrett
- Karen Devine
- Jordonna Fulop
- Quinn T. Ostrom
- Kristen Shimmel
- Yingli Wolinsky
- Andrew E. Sloan
- Agostino 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 J. Mural
- Stella Somiari
- Ales Vicha
- Tomas Zelinka
- Joseph Bennett
- Mary Iacocca
- Brenda Rabeno
- Patricia Swanson
- Mathieu Latour
- Louis Lacombe
- Bernard Têtu
- Alain Bergeron
- Mary McGraw
- Susan M. Staugaitis
- John Chabot
- Hanina Hibshoosh
- Antonia R. Sepulveda
- Tao Su
- Tim Wang
- Olga Potapova
- Olga Voronina
- L. Desjardins
- Odette Mariani
- Sergio Roman-Roman
- Xavier Sastre
- Marc-Henri Stern
- Feixiong Cheng
- Sabina Signoretti
- Andrew Berchuck
- Darell D. Bigner
- Eric Lipp
- Jeffrey R. Marks
- Shannon McCall
- Roger E. McLendon
- Angeles Alvarez Secord
- Alexis Sharp
- Madhusmita Behera
- Daniel J. Brat
- Amy Chen
- Keith 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 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
- John Houck
- Pawadee Lohavanichbutr
- Arndt Hartmann
- Christine Stoehr
- Robert Stoehr
- Helge Taubert
- Sven Wach
- Bernd Wullich
- Witold Kycler
- Dawid Murawa
- Maciej Wiznerowicz
- Ki Chung
- W. Jeffrey Edenfield
- Julie Martin
- Eric 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
- Elias Campo
- Eva Giné
- Armando López Guillermo
- Nguyen Van Bang
- Phan Thi Hanh
- Bui Duc Phu
- 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 Chandan
- John C. Cheville
- John A Iii Copland
- Michael B. Farnell
- Thomas J. Flotte
- Nasra H. Giama
- Thai Huu Ho
- Michael L. Kendrick
- Jean-Pierre Kocher
- Karla Kopp
- Catherine D. Moser
- David M. Nagorney
- Daniel O'Brien
- Brian Patrick O’Neill
- Tushar Patel
- Gloria M. Petersen
- Florencia G. Que
- Michael Rivera
- Lewis Rowland Roberts
- Robert Christian Smallridge
- Thomas Christopher Smyrk
- Melissa Stanton
- R. Houston Thompson
- Michael Torbenson
- Ju Dong Yang
- Lizhi Zhang
- Fadi Brimo
- Jaffer A. Ajani
- Ana Maria Angulo Gonzalez
- Carmen Behrens
- Jolanta Bondaruk
- Russell Broaddus
- Bogdan Czerniak
- Bita Esmaeli
- Junya Fujimoto
- Jeffrey E. Gershenwald
- Charles Chuanhai Guo
- Alexander J. Lazar
- Christopher J. Logothetis
- Funda Meric-Bernstam
- Cesar A. Moran
- Lois M Ramondetta
- David Rice
- Anil K. Sood
- Pheroze Tamboli
- Timothy C. Thompson
- Patricia Troncoso
- Anne Tsao
- Ignacio Ivan Wistuba
- Candace Carter
- Lauren E. Haydu
- Peter Hersey
- Valerie Jakrot
- Hojabr Kakavand
- Richard F. Kefford
- Kenneth Lee
- Georgina V. Long
- Graham J. Mann
- Michael Quinn
- Robyn Saw
- Richard A. Scolyer
- Kerwin Shannon
- Andrew Spillane
- Jonathan R. Stretch
- Maria Synott
- John F. Thompson
- James S. Wilmott
- Hikmat Al-Ahmadie
- Timothy A. Chan
- Ronald Ghossein
- Anuradha Gopalan
- Douglas A. Levine
- Victor E. Reuter
- Samuel Singer
- Bhuvanesh Singh
- Nguyen Viet Tien
- Thomas Broudy
- Cyrus Mirsaidi
- Praveen Nair
- Paul Drwiega
- Judy Miller
- Jennifer A. Smith
- Howard Zaren
- Joong Won Park
- Nguyen Phi Hung
- Electron Kebebew
- W. Marston Linehan
- Adam R. Metwalli
- Karel Pacak
- Peter A. Pinto
- Mark Schiffman
- Laura S. Schmidt
- Cathy D. Vocke
- Nicolas Wentzensen
- Robert Worrell
- Hannah P. Yang
- Marc Moncrieff
- Chandra Goparaju
- Jonathan Melamed
- Harvey I. Pass
- Natalia Botnariuc
- Irina Caraman
- Mircea Cernat
- Inga Chemencedji
- Adrian Clipca
- Serghei Doruc
- Ghenadie Gorincioi
- Sergiu Mura
- Maria Pirtac
- Irina Stancul
- Diana Tcaciuc
- Monique Albert
- Iakovina Alexopoulou
- Angel Arnaout
- John Bartlett
- Jay Engel
- Sebastien Gilbert
- Jeremy Parfitt
- Harman Sekhon
- George Thomas
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- Robert C. Rintoul
- Carlo Bifulco
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- Walter J. Urba
- Nicholas K. Hayward
- Henri Timmers
- Anna Antenucci
- Francesco Facciolo
- Gianluca Grazi
- Mirella Marino
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- Ronald R. de Krijger
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- Alain Piché
- Simone Chevalier
- Ginette McKercher
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- Gene Barnett
- Cathy Brewer
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- Vincenzo Cardinale
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- Antonio Jimeno
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- Massimo Mannelli
- Michael E. Carney
- Brenda Y. Hernandez
- Benito Campos
- Christel Herold-Mende
- Christin Jungk
- Andreas Unterberg
- Andreas von Deimling
- Aaron Bossler
- Joseph Galbraith
- Laura Jacobus
- Michael Knudson
- Tina Knutson
- Deqin Ma
- Mohammed M. Milhem
- Rita Sigmund
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- Howard G. Rosenthal
- Clement Adebamowo
- Sally N. Adebamowo
- Alex Boussioutas
- David G. Beer
- Thomas P. Giordano
- Anne-Marie Mes-Masson
- Fred Saad
- Therese Bocklage
- Lisa M. Landrum
- Robert S. Mannel
- Kathleen N. Moore
- Katherine Moxley
- Russel Postier
- Joan L. Walker
- Rosemary Zuna
- Michael 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 Tirapelli
- James Catto
- Kathy Agnew
- Elizabeth M. Swisher
- Jenette Creaney
- Bruce G. Robinson
- Carl Simon Shelley
- Eryn M. Godwin
- Sara Kendall
- Cassaundra Shipman
- Carol R. Bradford
- Thomas E. Carey
- Andrea Haddad
- Jeffey Moyer
- Lisa Peterson
- Mark E. Prince
- Laura S. Rozek
- Gregory T. Wolf
- Rayleen Bowman
- Kwun M. Fong
- Ian A. Yang
- Robert Korst
- W. Kimryn Rathmell
- J. Leigh Fantacone-Campbell
- Jeffrey A. Hooke
- Albert J. Kovatich
- John F. DiPersio
- Bettina F. Drake
- Ramaswamy Govindan
- Sharon Heath
- Timothy J. Ley
- Brian A. Van Tine
- Peter Westervelt
- Mark A. Rubin
- Jung-Il Lee
- Natália D. Aredes
- Armaz Mariamidze
- Helen Piwnica-Worms
- Li Ma
Summary 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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