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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Comprehensive Characterization of Cancer Driver Genes and Mutations
Cell, Volume 173, No. 2, Year 2018
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Description
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. © 2018
Authors & Co-Authors
Bertrand, Denis
Singapore, Singapore City
A-star, Genome Institute of Singapore
Kim, Jaegil
United States, Cambridge
Broad Institute
Reardon, Brendan
United States, Cambridge
Broad Institute
United States, Boston
Dana-farber Cancer Institute
Cao, Song
United States, St. Louis
Washington University in St. Louis
Nagarajan, Niranjan
Singapore, Singapore City
A-star, Genome Institute of Singapore
Cortes-Ciriano, Isidro
United States, Boston
Harvard Medical School
United States, Cambridge
Harvard University
United Kingdom, Cambridge
University of Cambridge
Park, Peter J.
United States, Boston
Harvard Medical School
United States, Cambridge
Harvard University
van Allen, Eliezer M.
United States, Cambridge
Broad Institute
United States, Boston
Dana-farber Cancer Institute
Liang, Han
United States, Houston
The University of Texas Md Anderson Cancer Center
Caesar-Johnson, Samantha J.
Unknown Affiliation
Demchok, John A.
Unknown Affiliation
Felau, Ina
Unknown Affiliation
Kasapi, Melpomeni
Unknown Affiliation
Ferguson, Martin L.
Unknown Affiliation
Hutter, Carolyn M.
Unknown Affiliation
Sofia, Heidi J.
Unknown Affiliation
Tarnuzzer, Roy W.
Unknown Affiliation
Zenklusen, Jean Claude
Unknown Affiliation
Chudamani, Sudha
Unknown Affiliation
Liu, Jia
Unknown Affiliation
Lolla, Laxmi
Unknown Affiliation
Naresh, Rashi
Unknown Affiliation
Pihl, Todd D.
Unknown Affiliation
Sun, Qiang
Unknown Affiliation
Wan, Yunhu
Unknown Affiliation
Wu, Ye
Unknown Affiliation
Cho, Juok
Unknown Affiliation
DeFreitas, Timothy
Unknown Affiliation
Frazer, Scott
Unknown Affiliation
Gehlenborg, Nils
Unknown Affiliation
Getz, Gad A.
United States, Cambridge
Broad Institute
Heiman, David I.
Unknown Affiliation
Lawrence, Michael S.
United States, Cambridge
Broad Institute
United States, Boston
Massachusetts General Hospital Cancer Center
Lin, Pei
Unknown Affiliation
Meier, Samuel R.
Unknown Affiliation
Noble, Michael S.
Unknown Affiliation
Saksena, Gordon
Unknown Affiliation
Voet, Doug
Unknown Affiliation
Bernard, Brady M.
Unknown Affiliation
Chambwe, Nyasha
Unknown Affiliation
Dhankani, Varsha
Unknown Affiliation
Knijnenburg, Theo A.
Unknown Affiliation
Kramer, Roger W.
Unknown Affiliation
Leinonen, Kalle
Unknown Affiliation
Liu, Yuexin
Unknown Affiliation
Miller, Michael B.
Unknown Affiliation
Reynolds, Sheila M.
Unknown Affiliation
Shmulevich, Ilya
Unknown Affiliation
Thorsson, Vesteinn
Unknown Affiliation
Zhang, Wei
Unknown Affiliation
Akbani, Rehan
Unknown Affiliation
Broom, Bradley M.
Unknown Affiliation
Hegde, Apurva M.
Unknown Affiliation
Ju, Zhenlin
Unknown Affiliation
Kanchi, Rupa S.
Unknown Affiliation
Korkut, Anil
Unknown Affiliation
Li, Jun
Unknown Affiliation
Ling, Shiyun
Unknown Affiliation
Liu, Wenbin
Unknown Affiliation
Lu, Yiling
Unknown Affiliation
Mills, Gordon B.
United States, Houston
The University of Texas Md Anderson Cancer Center
Ng, Kwokshing
Unknown Affiliation
Rao, Arvind U.K.
Unknown Affiliation
Ryan, Michael C.
Unknown Affiliation
Armenia, Joshua
Unknown Affiliation
Chatila, Walid K.
Unknown Affiliation
de Bruijn, Ino
Unknown Affiliation
Sánchez-Vega, Francisco
Unknown Affiliation
Schultz, Nikolaus D.
Unknown Affiliation
Yau, Christina
Unknown Affiliation
Parker, Joel S.
Unknown Affiliation
Wilkerson, Matthew D.
Unknown Affiliation
Bowlby, Reanne
Unknown Affiliation
Brooks, Denise B.
Unknown Affiliation
Jones, Steven J.M.
Unknown Affiliation
Ma, Yussanne P.
Unknown Affiliation
Marra, Marco A.
Unknown Affiliation
Moore, Richard A.
Unknown Affiliation
Mungall, Andrew J.
Unknown Affiliation
Mungall, Karen L.
Unknown Affiliation
Robertson, Andrew Gordon
Unknown Affiliation
Schein, Jacqueline E.
Unknown Affiliation
Berger, Ashton C.
Unknown Affiliation
Beroukhim, Rameen
Unknown Affiliation
Cherniack, Andrew D.
Unknown Affiliation
Gabriel, Stacey Bolk
Unknown Affiliation
Ha, Gavin
Unknown Affiliation
Schumacher, Steven E.
Unknown Affiliation
Xu, Jian M.
Unknown Affiliation
van den Berg, David J.
Unknown Affiliation
Hoadley, Katherine A.
Unknown Affiliation
Jones, Corbin D.
Unknown Affiliation
Roach, Jeffrey M.
Unknown Affiliation
Fan, Huihui
Unknown Affiliation
Laird, Peter W.
Unknown Affiliation
Shen, Hui
Unknown Affiliation
Chang, Kyle
Unknown Affiliation
Creighton, Chad J.
Unknown Affiliation
Dinh, Huyen H.
Unknown Affiliation
Doddapaneni, Harshavardhan
Unknown Affiliation
Drummond, Jennifer A.
Unknown Affiliation
Gibbs, Richard A.L.
Unknown Affiliation
Hale, Walker
Unknown Affiliation
Han, Yi
Unknown Affiliation
Korchina, Viktoriya
Unknown Affiliation
Lee, Sandra L.
Unknown Affiliation
Lewis, Lora R.
Unknown Affiliation
Li, Wei
Unknown Affiliation
Morgan, Margaret B.
Unknown Affiliation
Muzny, Donna Marie
Unknown Affiliation
Wang, Linghua
Unknown Affiliation
Fronick, Catrina C.
Unknown Affiliation
Fulton, Robert S.
Unknown Affiliation
Mardis, Elaine R.
Unknown Affiliation
Wilson, Richard K.
Unknown Affiliation
Paulauskis, Joseph D.
Unknown Affiliation
Bowen, Jay
Unknown Affiliation
Gastier-Foster, Julie M.
Unknown Affiliation
Lichtenberg, Tara M.
Unknown Affiliation
Ramirez, Nilsa C.
Unknown Affiliation
Zmuda, Erik J.
Unknown Affiliation
Corcoran, Niall M.
Unknown Affiliation
Hovens, Christopher M.
Unknown Affiliation
Humberto Fregnani, Jose
Unknown Affiliation
Longatto-Filho, Adhemar
Unknown Affiliation
Reis, Rui Manuel Vieira
Unknown Affiliation
Castro, Patricia D.
Unknown Affiliation
Ittmann, Michael M.
Unknown Affiliation
Huntsman, David G.
Unknown Affiliation
Warnick, Ronald E.
Unknown Affiliation
Cramer, Daniel William
Unknown Affiliation
Kibel, Adam S.
Unknown Affiliation
Barnholtz-Sloan, Jill S.
Unknown Affiliation
De Rose, Agostino Maria
Unknown Affiliation
Giuliante, Felice
Unknown Affiliation
Goodman, Marc T.
Unknown Affiliation
Karlan, Beth Y.
Unknown Affiliation
Somiari, Stella B.
Unknown Affiliation
Lacombe, Louis
Unknown Affiliation
Chabot, John A.
Unknown Affiliation
Desjardins, Laurence C.
Unknown Affiliation
Sastre-Garau, Xavier X.
Unknown Affiliation
Stern, Marc Henri
Unknown Affiliation
Signoretti, Sabina
Unknown Affiliation
Berchuck, Andrew
Unknown Affiliation
Brat, Daniel J.
Unknown Affiliation
Delman, Keith A.
Unknown Affiliation
Khuri, Fadlo R.
Unknown Affiliation
Magliocca, Kelly R.
Unknown Affiliation
Owonikoko, Taofeek Kunle
Unknown Affiliation
Ramalingam, Suresh S.
Unknown Affiliation
Shin, Dongmoon
Unknown Affiliation
Looijenga, Leendert H.J.
Unknown Affiliation
Oosterhuis, Wolter J.W.
Unknown Affiliation
Chen, Chu
Unknown Affiliation
Houck, John
Unknown Affiliation
Hartmann, Arndt
Unknown Affiliation
Stoehr, Robert
Unknown Affiliation
Wullich, Bernd
Unknown Affiliation
Noushmehr, Houtan
Unknown Affiliation
Girard, Nicolas
Unknown Affiliation
Campo, Elías
Unknown Affiliation
Colman, Howard
Unknown Affiliation
Martignetti, John A.
Unknown Affiliation
Gabra, H.
Unknown Affiliation
Akeredolu, Teniola
Unknown Affiliation
Birrer, Michael J.
Unknown Affiliation
Borad, Mitesh J.
Unknown Affiliation
Copland, John A.
Unknown Affiliation
Ho, Thai Huu
Unknown Affiliation
Patel, Tushar P.
Unknown Affiliation
Olson, Gloria Moy
Unknown Affiliation
Roberts, Lewis Rowland
Unknown Affiliation
Smallridge, Robert C.
Unknown Affiliation
Torbenson, Michael S.
Unknown Affiliation
Yang, Ju Dong
Unknown Affiliation
Brimo, Fadi
Unknown Affiliation
Fujimoto, Jyunya
Unknown Affiliation
Lazar, A. J.
United States, Houston
The University of Texas Md Anderson Cancer Center
Logothetis, Christopher J.
Unknown Affiliation
Meric-Bernstam, Funda
Unknown Affiliation
Moran, César A.
Unknown Affiliation
Rimner, Andreas C.
Unknown Affiliation
Sood, Anil K.
Unknown Affiliation
Tamboli, Pheroze
Unknown Affiliation
Tsao, Anne S.
Unknown Affiliation
Wistuba, Ignacio Ivans
Unknown Affiliation
Lee, Kenneth K.W.
Unknown Affiliation
Long, Georgina V.
Unknown Affiliation
Scolyer, Richard A.
Unknown Affiliation
Spillane, Andrew John
Unknown Affiliation
Wilmott, James S.
Unknown Affiliation
Chan, Timothy A.
Unknown Affiliation
Levine, Douglas A.
Unknown Affiliation
Smith, Jennifer Anne
Unknown Affiliation
Kebebew, Electron K.
Unknown Affiliation
Linehan, W. Marston
Unknown Affiliation
Pacak, Karel
Unknown Affiliation
Pinto, Peter A.
Unknown Affiliation
Schiffman, Mark H.
Unknown Affiliation
Wentzensen, Nicolas A.
Unknown Affiliation
Pass, Harvey Ira
Unknown Affiliation
Bartlett, John M.S.
Unknown Affiliation
Gilbert, Sebastien
Unknown Affiliation
Sekhon, Harman S.
Unknown Affiliation
Hayward, Nicholas K.
Unknown Affiliation
Gimenez-Roqueplo, Anne Paule
Unknown Affiliation
Birsoy, Kivanç
Unknown Affiliation
Barnett, Gene H.
Unknown Affiliation
Brewer, Cathy J.
Unknown Affiliation
Farver, Carol F.
Unknown Affiliation
Pennell, Nathan A.
Unknown Affiliation
Morrison, Carl D.
Unknown Affiliation
Omberg, Larsson
Unknown Affiliation
Manikhas, Georgiy Moiseevich
Unknown Affiliation
Alvaro, Domenico
Unknown Affiliation
Cardinale, Vincenzo
Unknown Affiliation
Dubina, Michael V.
Unknown Affiliation
Dhanasekaran, Renumathy
Unknown Affiliation
Slotta-Huspenina, Julia B.
Unknown Affiliation
Abdel-Rahman, Mohamed H.
Unknown Affiliation
Cebulla, Colleen M.
Unknown Affiliation
Lehman, Norman L.
Unknown Affiliation
Pilarski, Robert T.
Unknown Affiliation
Rai, Karan
Unknown Affiliation
Schoenfield, Lynn R.
Unknown Affiliation
Grizzle, William E.
Unknown Affiliation
Porten, Sima P.
Unknown Affiliation
Asa, Sylvia L.
Unknown Affiliation
Schadendorf, Dirk
Unknown Affiliation
Graefen, Markus
Unknown Affiliation
Huland, Hartwig
Unknown Affiliation
Sauter, Guido
Unknown Affiliation
Schlomm, Thorsten
Unknown Affiliation
Simon, Ronald
Unknown Affiliation
Tennstedt, Pierre
Unknown Affiliation
Bathe, Oliver F.
Unknown Affiliation
Carroll, Peter R.
Unknown Affiliation
Chan, June Maylin L.
Unknown Affiliation
DiSaia, Philip John
Unknown Affiliation
Kelley, Robin Kate
Unknown Affiliation
Phillips, Joanna J.
Unknown Affiliation
Simko, Jeffry P.
Unknown Affiliation
Smith-McCune, Karen K.
Unknown Affiliation
Carney, Michael E.
Unknown Affiliation
Hernandez, Brenda Y.
Unknown Affiliation
Herold-Mende, Christel C.
Unknown Affiliation
Unterberg, Andreas Wilhelm
Unknown Affiliation
von Deimling, Andreas
Unknown Affiliation
Godwin, Andrew K.
Unknown Affiliation
Adebamowo, Clement
Unknown Affiliation
Adebamowo, Sally N.
Unknown Affiliation
Boussioutas, Alex
Unknown Affiliation
Mès-Masson, Anne Marie
Unknown Affiliation
Saad, Fred
Unknown Affiliation
Moore, Kathleen Nadine
Unknown Affiliation
Walker, Joan L.
Unknown Affiliation
Feldman, Michael D.
Unknown Affiliation
Dhir, Rajiv J.
Unknown Affiliation
Luketich, James D.
Unknown Affiliation
Agnew, Kathy J.
Unknown Affiliation
Creaney, Jenette
Unknown Affiliation
Robinson, Bruce Gregory
Unknown Affiliation
Shelley, Carl Simon
Unknown Affiliation
Bradford, Carol R.
Unknown Affiliation
Carey, Thomas E.
Unknown Affiliation
Fong, Kwun Meng
Unknown Affiliation
Yang, Ian A.
Unknown Affiliation
Hooke, Jeffrey A.
Unknown Affiliation
Kovatich, Albert J.
Unknown Affiliation
Shriver, Craig D.
Unknown Affiliation
DIpersio, John F.
Unknown Affiliation
Drake, Bettina Fisher
Unknown Affiliation
Van Tine, Brian A.
Unknown Affiliation
Rubin, Mark A.
Unknown Affiliation
Godzik, Adam
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Wheeler, David A.
United States, Houston
Baylor College of Medicine
Statistics
Citations: 1,125
Authors: 277
Affiliations: 21
Identifiers
Doi:
10.1016/j.cell.2018.02.060
ISSN:
00928674
Research Areas
Cancer
Study Design
Cross Sectional Study