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Pan-cancer proteogenomics connects oncogenic drivers to functional states.
Li, Yize; Porta-Pardo, Eduard; Tokheim, Collin; Bailey, Matthew H; Yaron, Tomer M; Stathias, Vasileios; Geffen, Yifat; Imbach, Kathleen J; Cao, Song; Anand, Shankara; Akiyama, Yo; Liu, Wenke; Wyczalkowski, Matthew A; Song, Yizhe; Storrs, Erik P; Wendl, Michael C; Zhang, Wubing; Sibai, Mustafa; Ruiz-Serra, Victoria; Liang, Wen-Wei; Terekhanova, Nadezhda V; Rodrigues, Fernanda Martins; Clauser, Karl R; Heiman, David I; Zhang, Qing; Aguet, Francois; Calinawan, Anna P; Dhanasekaran, Saravana M; Birger, Chet; Satpathy, Shankha; Zhou, Daniel Cui; Wang, Liang-Bo; Baral, Jessika; Johnson, Jared L; Huntsman, Emily M; Pugliese, Pietro; Colaprico, Antonio; Iavarone, Antonio; Chheda, Milan G; Ricketts, Christopher J; Fenyö, David; Payne, Samuel H; Rodriguez, Henry; Robles, Ana I; Gillette, Michael A; Kumar-Sinha, Chandan; Lazar, Alexander J; Cantley, Lewis C; Getz, Gad; Ding, Li.
Affiliation
  • Li Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Porta-Pardo E; Josep Carreras Leukaemia Research Institute (IJC), Badalona 08916, Spain; Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.
  • Tokheim C; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Bailey MH; Department of Biology and Simmons Center for Cancer Research, Brigham Young University, Provo, UT 84602, USA.
  • Yaron TM; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA; Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Stathias V; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Geffen Y; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA.
  • Imbach KJ; Josep Carreras Leukaemia Research Institute (IJC), Badalona 08916, Spain; Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.
  • Cao S; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Anand S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Akiyama Y; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Liu W; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Wyczalkowski MA; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Song Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Storrs EP; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Wendl MC; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Zhang W; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Sibai M; Josep Carreras Leukaemia Research Institute (IJC), Badalona 08916, Spain; Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.
  • Ruiz-Serra V; Josep Carreras Leukaemia Research Institute (IJC), Badalona 08916, Spain; Barcelona Supercomputing Center (BSC), Barcelona 08034, Spain.
  • Liang WW; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Terekhanova NV; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Rodrigues FM; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Clauser KR; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Heiman DI; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Zhang Q; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Aguet F; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Calinawan AP; Department of Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Dhanasekaran SM; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Birger C; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Satpathy S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Zhou DC; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Wang LB; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Baral J; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
  • Johnson JL; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Huntsman EM; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • Pugliese P; Department of Science and Technology, University of Sannio, 82100 Benevento, Italy.
  • Colaprico A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Iavarone A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Neurological Surgery, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Chheda MG; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Ricketts CJ; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Fenyö D; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Payne SH; Department of Biology, Brigham Young University, Provo, UT 84602, USA.
  • Rodriguez H; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
  • Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
  • Gillette MA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Kumar-Sinha C; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Lazar AJ; Departments of Pathology & Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Cantley LC; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address: lewis_cantley@dfci.harvard.edu.
  • Getz G; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: gadgetz@broadinstitute.org.
  • Ding L; Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63130, USA; Siteman Cancer Center, Washington Univ
Cell ; 186(18): 3921-3944.e25, 2023 08 31.
Article in En | MEDLINE | ID: mdl-37582357
ABSTRACT
Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteogenomics / Neoplasms Limits: Humans Language: En Journal: Cell Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteogenomics / Neoplasms Limits: Humans Language: En Journal: Cell Year: 2023 Document type: Article Affiliation country: