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Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.
Gillette, Michael A; Satpathy, Shankha; Cao, Song; Dhanasekaran, Saravana M; Vasaikar, Suhas V; Krug, Karsten; Petralia, Francesca; Li, Yize; Liang, Wen-Wei; Reva, Boris; Krek, Azra; Ji, Jiayi; Song, Xiaoyu; Liu, Wenke; Hong, Runyu; Yao, Lijun; Blumenberg, Lili; Savage, Sara R; Wendl, Michael C; Wen, Bo; Li, Kai; Tang, Lauren C; MacMullan, Melanie A; Avanessian, Shayan C; Kane, M Harry; Newton, Chelsea J; Cornwell, MacIntosh; Kothadia, Ramani B; Ma, Weiping; Yoo, Seungyeul; Mannan, Rahul; Vats, Pankaj; Kumar-Sinha, Chandan; Kawaler, Emily A; Omelchenko, Tatiana; Colaprico, Antonio; Geffen, Yifat; Maruvka, Yosef E; da Veiga Leprevost, Felipe; Wiznerowicz, Maciej; Gümüs, Zeynep H; Veluswamy, Rajwanth R; Hostetter, Galen; Heiman, David I; Wyczalkowski, Matthew A; Hiltke, Tara; Mesri, Mehdi; Kinsinger, Christopher R; Boja, Emily S; Omenn, Gilbert S.
Afiliación
  • Gillette MA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02115, USA. Electronic address: gillette@broadinstitute.org.
  • Satpathy S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address: shankha@broadinstitue.org.
  • Cao S; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Dhanasekaran SM; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Vasaikar SV; Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Krug K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • Petralia F; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Li Y; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Liang WW; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Reva B; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Krek A; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ji J; Department of Population Health Science and Policy; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Song X; Department of Population Health Science and Policy; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Liu W; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Hong R; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Yao L; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Blumenberg L; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Savage SR; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Wendl MC; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Wen B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Li K; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Tang LC; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.
  • MacMullan MA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90089, USA.
  • Avanessian SC; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • Kane MH; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • Newton CJ; Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
  • Cornwell M; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Kothadia RB; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • Ma W; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Yoo S; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Mannan R; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Vats P; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Kumar-Sinha C; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Kawaler EA; Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Omelchenko T; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • Colaprico A; Department of Public Health Sciences, 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.
  • Maruvka YE; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • da Veiga Leprevost F; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Wiznerowicz M; Poznan University of Medical Sciences, Poznan, 61-701, Poland; International Institute for Molecular Oncology, Poznan, 60-203, Poland.
  • Gümüs ZH; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Veluswamy RR; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hostetter G; Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
  • Heiman DI; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
  • Wyczalkowski MA; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Hiltke T; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
  • Mesri M; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
  • Kinsinger CR; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
  • Boja ES; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
  • Omenn GS; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Cell ; 182(1): 200-225.e35, 2020 07 09.
Article en En | MEDLINE | ID: mdl-32649874
ABSTRACT
To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteogenómica / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteogenómica / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article