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Comprehensive Characterization of Cancer Driver Genes and Mutations.
Bailey, Matthew H; Tokheim, Collin; Porta-Pardo, Eduard; Sengupta, Sohini; Bertrand, Denis; Weerasinghe, Amila; Colaprico, Antonio; Wendl, Michael C; Kim, Jaegil; Reardon, Brendan; Ng, Patrick Kwok-Shing; Jeong, Kang Jin; Cao, Song; Wang, Zixing; Gao, Jianjiong; Gao, Qingsong; Wang, Fang; Liu, Eric Minwei; Mularoni, Loris; Rubio-Perez, Carlota; Nagarajan, Niranjan; Cortés-Ciriano, Isidro; Zhou, Daniel Cui; Liang, Wen-Wei; Hess, Julian M; Yellapantula, Venkata D; Tamborero, David; Gonzalez-Perez, Abel; Suphavilai, Chayaporn; Ko, Jia Yu; Khurana, Ekta; Park, Peter J; Van Allen, Eliezer M; Liang, Han; Lawrence, Michael S; Godzik, Adam; Lopez-Bigas, Nuria; Stuart, Josh; Wheeler, David; Getz, Gad; Chen, Ken; Lazar, Alexander J; Mills, Gordon B; Karchin, Rachel; Ding, Li.
Afiliación
  • Bailey MH; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Tokheim C; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Porta-Pardo E; Barcelona Supercomputing Centre (BSC), Barcelona, Spain; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Sengupta S; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Bertrand D; Computational and Systems Biology, Genome Institute of Singapore, Singapore, 138672.
  • Weerasinghe A; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Colaprico A; Interuniversity Institute of Bioinformatics in Brussels (IB()2), 1050 Brussels, Belgium; Machine Learning Group (MLG), Département d'Informatique, Université Libre de Bruxelles (ULB), Boulevard du Triomphe, CP212, 1050 Bruxelles, Belgium; Department of Human Genetics, University of Miami, Miller Sch
  • Wendl MC; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA; Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Kim J; The Broad Institute, Cambridge, MA 02142, USA.
  • Reardon B; The Broad Institute, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ng PK; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jeong KJ; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Cao S; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Wang Z; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Gao J; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Gao Q; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Wang F; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Liu EM; Meyer Cancer Center and Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
  • Mularoni L; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
  • Rubio-Perez C; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
  • Nagarajan N; Computational and Systems Biology, Genome Institute of Singapore, Singapore, 138672.
  • Cortés-Ciriano I; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Boston, MA 02115, USA; Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
  • Zhou DC; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Liang WW; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Hess JM; The Broad Institute, Cambridge, MA 02142, USA.
  • Yellapantula VD; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Tamborero D; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
  • Gonzalez-Perez A; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
  • Suphavilai C; Computational and Systems Biology, Genome Institute of Singapore, Singapore, 138672.
  • Ko JY; Computational and Systems Biology, Genome Institute of Singapore, Singapore, 138672.
  • Khurana E; Meyer Cancer Center and Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
  • Park PJ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Boston, MA 02115, USA.
  • Van Allen EM; The Broad Institute, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Liang H; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lawrence MS; The Broad Institute, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114, USA.
  • Godzik A; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Lopez-Bigas N; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
  • Stuart J; University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
  • Wheeler D; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Getz G; The Broad Institute, Cambridge, MA 02142, USA.
  • Chen K; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lazar AJ; Departments of Pathology, Genomic Medicine, & Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mills GB; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Karchin R; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: karchin@jhu.edu.
  • Ding L; Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washin
Cell ; 173(2): 371-385.e18, 2018 04 05.
Article en En | MEDLINE | ID: mdl-29625053
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Límite: Humans Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Límite: Humans Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos