ArticleCell2020
Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.
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Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 513 papers.
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513citing papers in PubMed
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Who cites it
513 citing papers in PubMed, 792 citations in OpenAlex.
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Authors and funding
69 authors at 20 institutions in 2 countries.
Michael A GilletteBroad 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.
Shankha SatpathyBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address: shankha@broadinstitue.org.
Song CaoDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Saravana M DhanasekaranDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Suhas V VasaikarDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, 77030, USA.
Karsten KrugBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Francesca PetraliaDepartment 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.
Yize LiDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Wen-Wei LiangDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Boris RevaDepartment 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.
Azra KrekDepartment 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.
Jiayi JiDepartment of Population Health Science and Policy; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Xiaoyu SongDepartment of Population Health Science and Policy; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Wenke LiuInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Runyu HongInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Lijun YaoDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Lili BlumenbergInstitute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Sara R SavageLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Michael C WendlDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Bo WenLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Kai LiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Lauren C TangBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.
Melanie A MacMullanBroad 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.
Shayan C AvanessianBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
M Harry KaneBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Chelsea J NewtonVan Andel Research Institute, Grand Rapids, MI, 49503, USA.
MacIntosh CornwellInstitute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Ramani B KothadiaBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Weiping MaDepartment 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.
Seungyeul YooDepartment 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.
Rahul MannanDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Pankaj VatsDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Chandan Kumar-SinhaDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Emily A KawalerInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Tatiana OmelchenkoSloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Antonio ColapricoDepartment of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA.
Yifat GeffenBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Yosef E MaruvkaBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Felipe da Veiga LeprevostDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Maciej WiznerowiczPoznan University of Medical Sciences, Poznań, 61-701, Poland; International Institute for Molecular Oncology, Poznań, 60-203, Poland.
Zeynep H GümüşDepartment 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.
Rajwanth R VeluswamyDivision of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Galen HostetterVan Andel Research Institute, Grand Rapids, MI, 49503, USA.
David I HeimanBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Matthew A WyczalkowskiDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
Tara HiltkeOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Mehdi MesriOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Christopher R KinsingerOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Emily S BojaOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Gilbert S OmennDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Arul M ChinnaiyanDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Henry RodriguezOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Qing Kay LiSidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD, 21224, USA.
Scott D JewellVan Andel Research Institute, Grand Rapids, MI, 49503, USA.
Mathangi ThiagarajanLeidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Gad GetzBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
David FenyöInstitute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Kelly V RugglesInstitute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Marcin P CieslikDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Ana I RoblesOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Karl R ClauserBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Ramaswamy GovindanDivision of Oncology and Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
Pei WangDepartment 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.
Alexey I NesvizhskiiDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Li DingDepartment of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
D R ManiBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA.
Steven A CarrBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address: scarr@broad.mit.edu.
Clinical Proteomic Tumor Analysis Consortium
Clinical Research Consortium · USFusion (United States) · USFusion Academy · USUniversity of Michigan–Ann Arbor · USWashington University in St. Louis · USIcahn School of Medicine at Mount Sinai · USInstitute for Systems Biology · USBroad Institute · USNational Cancer Institute · USBaylor College of Medicine · USMassachusetts Institute of Technology · USMemorial Sloan Kettering Cancer Center · USVan Andel Institute · USColumbia University · USSidney Kimmel Comprehensive Cancer Center · USThe University of Texas MD Anderson Cancer Center · USInternational Institute for Molecular Oncology · PLLeidos (United States) · USTisch Hospital · USUniversity of Miami · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MUsing Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Kalyani Pyaram, Steven Allan Soper · 2019 to 2026
$21.5MStrategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MCenter of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4MThe Comprehensive Proteome Characterization Center at Johns Hopkins: High Precision Discovery and Confirmation of Genoproteomic TargetsU24CA210985 · NCI · JOHNS HOPKINS UNIVERSITY · PI CHAN, DANIEL WANYUI, ZHANG, HUI · 2016 to 2020
$5.3MPNNL Proteome Characterization CenterU24CA210955 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI LIU, TAO, SMITH, RICHARD D · 2016 to 2020
$5.3MiPGDAC, An Integrative Proteogenomic Data Analysis Center for CPTACU24CA210954 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, BING · 2016 to 2020
$4.9MSystems Biology based Proteogenomic Translator for Cancer Marker Discovery towards Precision MedicineU24CA210993 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHADT, ERIC E, WANG, PEI · 2016 to 2020
$4.6MIntegrated high throughput proteogenomic data analysis center for CPTACU24CA210979 · NCI · BROAD INSTITUTE, INC. · PI BIRGER, CHET, GETZ, GAD A · 2016 to 2020
$4.4MUniversity of Michigan Proteogenomics Data Analysis CenterU24CA210967 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, DHANASEKARAN, SARAVANA M · 2016 to 2020
$4.1MNCI NIH HHS P30 CA008748NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210954NCI NIH HHS U24 CA210955NCI NIH HHS U24 CA210967NCI NIH HHS U24 CA210972NCI NIH HHS U24 CA210979NCI NIH HHS U24 CA210985NCI NIH HHS U24 CA210986NCI NIH HHS U24 CA210993NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P30 ES017885NIGMS NIH HHS P20 GM130423
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.
Indexed as
ProteogenomicsAdenocarcinoma of LungAdultAgedAged, 80 and overBiomarkers, TumorCarcinogenesisDNA Copy Number VariationsDNA MethylationFemaleHumansLung NeoplasmsMaleMiddle AgedMutationOncogene Proteins, FusionBiomarkers, TumorOncogene Proteins, FusionPhosphoproteinsProteomeacetylationadenocarcinomaCPTACgenomicslung cancermass spectrometryphosphorylationproteinproteogenomicsproteomics
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