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Comprehensive Characterization of Cancer Driver Genes and Mutations
Bailey M.H.1; Tokheim C.3; Porta-Pardo E.22; Sengupta S.1; Bertrand D.6; Weerasinghe A.1; Colaprico A.4; Wendl M.C.1; Kim J.11; Reardon B.11; Ng P.K.-S.2; Jeong K.J.2; Cao S.1; Wang Z.2; Gao J.17; Gao Q.1; Wang F.2; Liu E.M.7; Mularoni L.10; Rubio-Perez C.10; Nagarajan N.6; Cortes-Ciriano I.18; Zhou D.C.1; Liang W.-W.1; Hess J.M.11; Yellapantula V.D.1; Tamborero D.10; Gonzalez-Perez A.10; Suphavilai C.6; Ko J.Y.6; Khurana E.7; Park P.J.18; Van Allen E.M.11; Liang H.2; Caesar-Johnson S.J.; Demchok J.A.; Felau I.; Kasapi M.; Ferguson M.L.; Hutter C.M.; Sofia H.J.; Tarnuzzer R.; Yang L.; Zenklusen J.C.; Zhang J.J.; Chudamani S.; Liu J.; Lolla L.; Naresh R.; Pihl T.; Sun Q.; Wan Y.; Wu Y.; Cho J.; DeFreitas T.; Frazer S.; Gehlenborg N.; Getz G.11; Heiman D.I.; Lawrence M.S.11; Lin P.; Meier S.; Noble M.S.; Saksena G.; Voet D.; Zhang H.; Bernard B.; Chambwe N.; Dhankani V.; Knijnenburg T.; Kramer R.; Leinonen K.; Liu Y.; Miller M.; Reynolds S.; Shmulevich I.; Thorsson V.; Zhang W.; Akbani R.; Broom B.M.; Hegde A.M.; Ju Z.; Kanchi R.S.; Korkut A.; Li J.; Ling S.; Liu W.; Lu Y.; Mills G.B.2; Ng K.-S.; Rao A.; Ryan M.; Wang J.; Weinstein J.N.; Zhang J.; Abeshouse A.; Armenia J.; Chakravarty D.; Chatila W.K.; de Bruijn I.; Gross B.E.; Heins Z.J.; Kundra R.; La K.; Ladanyi M.; Luna A.; Nissan M.G.; Ochoa A.; Phillips S.M.; Reznik E.; Sanchez-Vega F.; Sander C.; Schultz N.; Sheridan R.; Sumer S.O.; Sun Y.; Taylor B.S.; Anur P.; Peto M.; Spellman P.; Benz C.; Stuart J.M.; Wong C.K.; Yau C.; Hayes D.N.; Parker J.S.; Wilkerson M.D.; Ally A.; Balasundaram M.; Bowlby R.; Brooks D.; Carlsen R.; Chuah E.; Dhalla N.; Holt R.; Jones S.J.M.; Kasaian K.; Lee D.; Ma Y.; Marra M.A.; Mayo M.; Moore R.A.; Mungall A.J.; Mungall K.; Robertson A.G.; Sadeghi S.; Schein J.E.; Sipahimalani P.; Tam A.; Thiessen N.; Tse K.; Wong T.; Berger A.C.; Beroukhim R.; Cherniack A.D.; Cibulskis C.; Gabriel S.B.; Gao G.F.; Ha G.; Meyerson M.; Schumacher S.E.; Shih J.; Kucherlapati M.H.; Kucherlapati R.S.; Baylin S.; Cope L.; Danilova L.; Bootwalla M.S.; Lai P.H.; Maglinte D.T.; Van Den Berg D.J.; Weisenberger D.J.; Auman J.T.; Balu S.; Bodenheimer T.; Fan C.; Hoadley K.A.; Hoyle A.P.; Jefferys S.R.; Jones C.D.; Meng S.; Mieczkowski P.A.; Mose L.E.; Perou A.H.; Perou C.M.; Roach J.; Shi Y.; Simons J.V.; Skelly T.; Soloway M.G.; Tan D.; Veluvolu U.; Fan H.; Hinoue T.; Laird P.W.; Shen H.; Zhou W.; Bellair M.; Chang K.; Covington K.; Creighton C.J.; Dinh H.; Doddapaneni H.; Donehower L.A.; Drummond J.; Gibbs R.A.; Glenn R.; Hale W.; Han Y.; Hu J.; Korchina V.; Lee S.; Lewis L.; Li W.; Liu X.; Morgan M.; Morton D.; Muzny D.; Santibanez J.; Sheth M.; Shinbrot E.; Wang L.; Wang M.; Wheeler D.A.; Xi L.; Zhao F.; Hess J.; Appelbaum E.L.; Bailey M.; Cordes M.G.; Ding L.1; Fronick C.C.; Fulton L.A.; Fulton R.S.; Kandoth C.; Mardis E.R.; McLellan M.D.; Miller C.A.; Schmidt H.K.; Wilson R.K.; Crain D.; Curley E.; Gardner J.; Lau K.; Mallery D.; Morris S.; Paulauskis J.; Penny R.; Shelton C.; Shelton T.; Sherman M.; Thompson E.; Yena P.; Bowen J.; Gastier-Foster J.M.; Gerken M.; Leraas K.M.; Lichtenberg T.M.; Ramirez N.C.; Wise L.; Zmuda E.; Corcoran N.; Costello T.; Hovens C.; Carvalho A.L.; de Carvalho A.C.; Fregnani J.H.; Longatto-Filho A.; Reis R.M.; Scapulatempo-Neto C.; Silveira H.C.S.; Vidal D.O.; Burnette A.; Eschbacher J.; Hermes B.; Noss A.; Singh R.; Anderson M.L.; Castro P.D.; Ittmann M.; Huntsman D.; Kohl B.; Le X.; Thorp R.; Andry C.; Duffy E.R.; Lyadov V.; Paklina O.; Setdikova G.; Shabunin A.; Tavobilov M.; McPherson C.; Warnick R.; Berkowitz R.; Cramer D.; Feltmate C.; Horowitz N.; Kibel A.; Muto M.; Raut C.P.; Malykh A.; Barnholtz-Sloan J.S.; Barrett W.; Devine K.; Fulop J.; Ostrom Q.T.; Shimmel K.; Wolinsky Y.; Sloan A.E.; De Rose A.; Giuliante F.; Goodman M.; Karlan B.Y.; Hagedorn C.H.; Eckman J.; Harr J.; Myers J.; Tucker K.; Zach L.A.; Deyarmin B.; Hu H.; Kvecher L.; Larson C.; Mural R.J.; Somiari S.; Vicha A.; Zelinka T.; Bennett J.; Iacocca M.; Rabeno B.; Swanson P.; Latour M.; Lacombe L.; Tetu B.; Bergeron A.; McGraw M.; Staugaitis S.M.; Chabot J.; Hibshoosh H.; Sepulveda A.; Su T.; Wang T.; Potapova O.; Voronina O.; Desjardins L.; Mariani O.; Roman-Roman S.; Sastre X.; Stern M.-H.; Cheng F.; Signoretti S.; Berchuck A.; Bigner D.; Lipp E.; Marks J.; McCall S.; McLendon R.; Secord A.; Sharp A.; Behera M.; Brat D.J.; Chen A.; Delman K.; Force S.; Khuri F.; Magliocca K.; Maithel S.; Olson J.J.; Owonikoko T.; Pickens A.; Ramalingam S.; Shin D.M.; Sica G.; Van Meir E.G.; Eijckenboom W.; Gillis A.; Korpershoek E.; Looijenga L.; Oosterhuis W.; Stoop H.; van Kessel K.E.; Zwarthoff E.C.; Calatozzolo C.; Cuppini L.; Cuzzubbo S.; DiMeco F.; Finocchiaro G.; Mattei L.; Perin A.; Pollo B.; Chen C.; Houck J.; Lohavanichbutr P.; Hartmann A.; Stoehr C.; Stoehr R.; Taubert H.; Wach S.; Wullich B.; Kycler W.; Murawa D.; Wiznerowicz M.; Chung K.; Edenfield W.J.; Martin J.; Baudin E.; Bubley G.; Bueno R.; De Rienzo A.; Richards W.G.; Kalkanis S.; Mikkelsen T.; Noushmehr H.; Scarpace L.; Girard N.; Aymerich M.; Campo E.; Gine E.; Guillermo A.L.; Van Bang N.; Hanh P.T.; Phu B.D.; Tang Y.; Colman H.; Evason K.; Dottino P.R.; Martignetti J.A.; Gabra H.; Juhl H.; Akeredolu T.; Stepa S.; Hoon D.; Ahn K.; Kang K.J.; Beuschlein F.; Breggia A.; Birrer M.; Bell D.; Borad M.; Bryce A.H.; Castle E.; Chandan V.; Cheville J.; Copland J.A.; Farnell M.; Flotte T.; Giama N.; Ho T.; Kendrick M.; Kocher J.-P.; Kopp K.; Moser C.; Nagorney D.; O'Brien D.; O'Neill B.P.; Patel T.; Petersen G.; Que F.; Rivera M.; Roberts L.; Smallridge R.; Smyrk T.; Stanton M.; Thompson R.H.; Torbenson M.; Yang J.D.; Zhang L.; Brimo F.; Ajani J.A.; Gonzalez A.M.A.; Behrens C.; Bondaruk J.; Broaddus R.; Czerniak B.; Esmaeli B.; Fujimoto J.; Gershenwald J.; Guo C.; Lazar A.J.2; Logothetis C.; Meric-Bernstam F.; Moran C.; Ramondetta L.; Rice D.; Sood A.; Tamboli P.; Thompson T.; Troncoso P.; Tsao A.; Wistuba I.; Carter C.; Haydu L.; Hersey P.; Jakrot V.; Kakavand H.; Kefford R.; Lee K.; Long G.; Mann G.; Quinn M.; Saw R.; Scolyer R.; Shannon K.; Spillane A.; Stretch J.; Synott M.; Thompson J.; Wilmott J.; Al-Ahmadie H.; Chan T.A.; Ghossein R.; Gopalan A.; Levine D.A.; Reuter V.; Singer S.; Singh B.; Tien N.V.; Broudy T.; Mirsaidi C.; Nair P.; Drwiega P.; Miller J.; Smith J.; Zaren H.; Park J.-W.; Hung N.P.; Kebebew E.; Linehan W.M.; Metwalli A.R.; Pacak K.; Pinto P.A.; Schiffman M.; Schmidt L.S.; Vocke C.D.; Wentzensen N.; Worrell R.; Yang H.; Moncrieff M.; Goparaju C.; Melamed J.; Pass H.; Botnariuc N.; Caraman I.; Cernat M.; Chemencedji I.; Clipca A.; Doruc S.; Gorincioi G.; Mura S.; Pirtac M.; Stancul I.; Tcaciuc D.; Albert M.; Alexopoulou I.; Arnaout A.; Bartlett J.; Engel J.; Gilbert S.; Parfitt J.; Sekhon H.; Thomas G.; Rassl D.M.; Rintoul R.C.; Bifulco C.; Tamakawa R.; Urba W.; Hayward N.; Timmers H.; Antenucci A.; Facciolo F.; Grazi G.; Marino M.; Merola R.; de Krijger R.; Gimenez-Roqueplo A.-P.; Piche A.; Chevalier S.; McKercher G.; Birsoy K.; Barnett G.; Brewer C.; Farver C.; Naska T.; Pennell N.A.; Raymond D.; Schilero C.; Smolenski K.; Williams F.; Morrison C.; Borgia J.A.; Liptay M.J.; Pool M.; Seder C.W.; Junker K.; Omberg L.; Dinkin M.; Manikhas G.; Alvaro D.; Bragazzi M.C.; Cardinale V.; Carpino G.; Gaudio E.; Chesla D.; Cottingham S.; Dubina M.; Moiseenko F.; Dhanasekaran R.; Becker K.-F.; Janssen K.-P.; Slotta-Huspenina J.; Abdel-Rahman M.H.; Aziz D.; Bell S.; Cebulla C.M.; Davis A.; Duell R.; Elder J.B.; Hilty J.; Kumar B.; Lang J.; Lehman N.L.; Mandt R.; Nguyen P.; Pilarski R.; Rai K.; Schoenfield L.; Senecal K.; Wakely P.; Hansen P.; Lechan R.; Powers J.; Tischler A.; Grizzle W.E.; Sexton K.C.; Kastl A.; Henderson J.; Porten S.; Waldmann J.; Fassnacht M.; Asa S.L.; Schadendorf D.; Couce M.; Graefen M.; Huland H.; Sauter G.; Schlomm T.; Simon R.; Tennstedt P.; Olabode O.; Nelson M.; Bathe O.; Carroll P.R.; Chan J.M.; Disaia P.; Glenn P.; Kelley R.K.; Landen C.N.; Phillips J.; Prados M.; Simko J.; Smith-McCune K.; VandenBerg S.; Roggin K.; Fehrenbach A.; Kendler A.; Sifri S.; Steele R.; Jimeno A.; Carey F.; Forgie I.; Mannelli M.; Carney M.; Hernandez B.; Campos B.; Herold-Mende C.; Jungk C.; Unterberg A.; von Deimling A.; Bossler A.; Galbraith J.; Jacobus L.; Knudson M.; Knutson T.; Ma D.; Milhem M.; Sigmund R.; Godwin A.K.; Madan R.; Rosenthal H.G.; Adebamowo C.; Adebamowo S.N.; Boussioutas A.; Beer D.; Giordano T.; Mes-Masson A.-M.; Saad F.; Bocklage T.; Landrum L.; Mannel R.; Moore K.; Moxley K.; Postier R.; Walker J.; Zuna R.; Feldman M.; Valdivieso F.; Dhir R.; Luketich J.; Pinero E.M.M.; Quintero-Aguilo M.; Carlotti C.G.; Dos Santos J.S.; Kemp R.; Sankarankuty A.; Tirapelli D.; Catto J.; Agnew K.; Swisher E.; Creaney J.; Robinson B.; Shelley C.S.; Godwin E.M.; Kendall S.; Shipman C.; Bradford C.; Carey T.; Haddad A.; Moyer J.; Peterson L.; Prince M.; Rozek L.; Wolf G.; Bowman R.; Fong K.M.; Yang I.; Korst R.; Rathmell W.K.; Fantacone-Campbell J.L.; Hooke J.A.; Kovatich A.J.; Shriver C.D.; DiPersio J.; Drake B.; Govindan R.; Heath S.; Ley T.; Van Tine B.; Westervelt P.; Rubin M.A.; Lee J.I.; Aredes N.D.; Mariamidze A.; Godzik A.9; Lopez-Bigas N.7; Stuart J.20; Wheeler D.12; Chen K.2; Karchin R.3
2018-04-05
Source PublicationCell
ISSN10974172 00928674
Volume173Issue:2Pages:371-385.e18
Abstract

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. A comprehensive analysis of oncogenic driver genes and mutations in >9,000 tumors across 33 cancer types highlights the prevalence of clinically actionable cancer driver events in TCGA tumor samples.

KeywordDriver Gene Discovery Mutations Of Clinical Relevance Oncology Structure Analysis
DOI10.1016/j.cell.2018.02.060
URLView the original
Language英語English
WOS IDWOS:000429320200012
Scopus ID2-s2.0-85044623848
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Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Washington University in St. Louis
2.University of Texas MD Anderson Cancer Center
3.Johns Hopkins University
4.Interuniversity Institute of Bioinformatics in Brussels
5.Ludwig Center at Harvard
6.A-Star, Genome Institute of Singapore
7.Meyer Cancer Center
8.Massachusetts General Hospital Cancer Center
9.Sanford Burnham Prebys Medical Discovery Institute
10.IRB Barcelona - Institute for Research in Biomedicine
11.Broad Institute
12.Baylor College of Medicine
13.University of Miami Leonard M. Miller School of Medicine
14.University of Cambridge
15.Dana-Farber Cancer Institute
16.Washington University School of Medicine in St. Louis
17.Memorial Sloan-Kettering Cancer Center
18.Harvard Medical School
19.Université libre de Bruxelles (ULB)
20.University of California, Santa Cruz
21.Institucio Catalana de Recerca I Estudis Avancats
22.Centro Nacional de Supercomputación
Recommended Citation
GB/T 7714
Bailey M.H.,Tokheim C.,Porta-Pardo E.,et al. Comprehensive Characterization of Cancer Driver Genes and Mutations[J]. Cell, 2018, 173(2), 371-385.e18.
APA Bailey M.H.., Tokheim C.., Porta-Pardo E.., Sengupta S.., Bertrand D.., Weerasinghe A.., Colaprico A.., Wendl M.C.., Kim J.., Reardon B.., Ng P.K.-S.., Jeong K.J.., Cao S.., Wang Z.., Gao J.., Gao Q.., Wang F.., Liu E.M.., Mularoni L.., ...& Karchin R. (2018). Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell, 173(2), 371-385.e18.
MLA Bailey M.H.,et al."Comprehensive Characterization of Cancer Driver Genes and Mutations".Cell 173.2(2018):371-385.e18.
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