ArticleNature2016
Proteogenomics connects somatic mutations to signalling in breast cancer.
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Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 997 papers, 1 of them a synthesis that pooled it.
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997citing papers in PubMed, 1 pooled it
75.7field-weighted citation impact, top 1% of its field
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
997 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,730 citations in OpenAlex.
- Progress and trends on machine learning in proteomics during 1997-2024: a bibliometric analysis.Frontiers in medicine · 2025Pooled it
- Proteogenomic analysis of the CALGB 40601 (Alliance) HER2+ breast cancer neoadjuvant trial reveals resistance biomarkers.Cell reports. Medicine · 2025Trial
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- Integrating multi-omics data for next-generation cancer research and precision medicine.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
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- ESR1 mutations are associated with enhanced MTORC1 signaling in a context-dependent manner.Communications biology · 2026Article
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- A Review of Proteomic Studies in Uterine Leiomyosarcoma: Biomarkers, Pathways, and Clinical Potential.Current issues in molecular biology · 2026Review
- Multi-omics analysis reveals comprehensive aberrant protein and phosphorylation characteristics in breast cancer and paired metastatic lymph nodes.Protein & cell · 2026Article
- WNK1 Phosphorylation Sites in TBC1D1 and TBC1D4 Modulate Cell-Surface Abundance of GLUT1.Cells · 2026Article
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Druggable genome CRISPRi screen in hydrogels reveals regulators of cortactin-driven actin remodeling promoting glioblastoma invasion.JCI insight · 2026Article
- Protein Enrichment from Ascites Fluid Using Nanotrap Hydrogel Particle Technology.Journal of proteome research · 2026Article
- A molecular switch for coordinating kinesin and dynein transport of mitochondrial cargo.Science (New York, N.Y.) · 2026Article
- Proteomic Biomarker Discovery in Breast Cancer: Advances, Challenges, and Translational Prospects.Journal of biochemical and molecular toxicology · 2026Review
- Scalable phosphotyrosine enrichment with SH2 superbinder enables deep profiling of EGF responses.The EMBO journal · 2026Article
- Targeting UXS1-Dependent Glucuronate Detoxification Potentiates Metformin's Anti-Tumor Efficacy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
937 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 8 institutions in 2 countries.
Philipp MertinsThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
D R ManiThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Kelly V RugglesDepartment of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, New York 10016, USA.
Michael A GilletteThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Karl R ClauserThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Pei WangDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai New York, New York 10029, USA.
Xianlong WangFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Jana W QiaoThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Song CaoDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Francesca PetraliaDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai New York, New York 10029, USA.
Emily KawalerDepartment of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, New York 10016, USA.
Filip MundtThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Karsten KrugThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Zhidong TuDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai New York, New York 10029, USA.
Jonathan T LeiLester and Sue Smith Breast Center, Dan L. Duncan Comprehensive Cancer Center and Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Michael L GatzaDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Matthew WilkersonDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Charles M PerouDepartment of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Venkata YellapantulaDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Kuan-lin HuangDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Chenwei LinFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Michael D McLellanDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Ping YanFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Sherri R DaviesDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
R Reid TownsendDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Steven J SkatesBiostatistics Center, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA.
Jing WangDepartment of Biomedical Informatics and Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Bing ZhangDepartment of Biomedical Informatics and Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Christopher R KinsingerNational Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mehdi MesriNational Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Henry RodriguezNational Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Li DingDepartment of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Amanda G PaulovichFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
David FenyöDepartment of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, New York 10016, USA.
Matthew J EllisLester and Sue Smith Breast Center, Dan L. Duncan Comprehensive Cancer Center and Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Steven A CarrThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
NCI CPTAC
Broad Institute · USWashington University in St. Louis · USNational Institutes of Health · USUniversity of North Carolina at Chapel Hill · USBaylor College of Medicine · USFred Hutch Cancer Center · USNYU Langone Health · USVanderbilt University · US
Funding
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MWashington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4MWashington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4MProteo-genomic Discovery, Prioritization and Verification of Cancer BiomarkersU24CA160034 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, PAULOVICH, AMANDA G · 2011 to 2016
$16.2MYOGA LIFESTYLE INTERVENTION REDUCES BLOOD PRESSURE IN HIV-INFECTED ADULTSP41RR000954 · NCRR · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 1985 to 2011
$16.0MPNNL Clinical Proteome Characterization CenterU24CA160019 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI RODLAND, KARIN D, SMITH, RICHARD D · 2011 to 2016
$15.7MVanderbilt Proteome Characterization CenterU24CA159988 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LIEBLER, DANIEL C · 2011 to 2016
$13.9MTrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0MCancer Proteome Center at Washington Univ, Univ of North Carolina & Boise StateU24CA160035 · NCI · WASHINGTON UNIVERSITY · PI CHEN, XIAN, ELLIS, MATTHEW J · 2011 to 2016
$11.8MProteome Characterization Center: A Genoproteomics Pipeline for Cance ResearchU24CA160036 · NCI · JOHNS HOPKINS UNIVERSITY · PI CHAN, DANIEL WANYUI, ZHANG, HUI · 2011 to 2016
$10.7MIntegrative multivariate association and genomic analysesR01GM108711 · NIGMS · UNIVERSITY OF CHICAGO · PI CHEN, LIN · 2014 to 2022
$3.1MNCATS NIH HHS UL1 TR000448NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA091842NCI NIH HHS P30 CA91842NCI NIH HHS R00 CA166228NCI NIH HHS U24 CA159988NCI NIH HHS U24CA159988NCI NIH HHS U24 CA160019NCI NIH HHS U24CA160019NCI NIH HHS U24 CA160034NCI NIH HHS U24CA160034NCI NIH HHS U24 CA160035NCI NIH HHS U24CA160035NCI NIH HHS U24 CA160036NCI NIH HHS U24CA160036NCRR NIH HHS P41 RR000954NCRR NIH HHS RR140033NCRR NIH HHS UL1 RR024992NIGMS NIH HHS P41 GM103422NIGMS NIH HHS R01 GM108711NIGMS NIH HHS R01GM108711NIGMS NIH HHS T32 GM088129
Abstract
Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.
Indexed as
GenomicsProteomicsSignal TransductionBreast NeoplasmsCalcium-Binding ProteinsChromosome DeletionChromosomes, Human, Pair 5Class I Phosphatidylinositol 3-KinasesCyclin-Dependent KinasesErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleFocal Adhesion Kinase 1Gene Expression Regulation, NeoplasticHumansMass SpectrometryCalcium-Binding ProteinsCDK12 protein, humanCETN3 protein, humanClass I Phosphatidylinositol 3-KinasesCyclin-Dependent KinasesEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFocal Adhesion Kinase 1p21-Activated KinasesPAK1 protein, humanPhosphatidylinositol 3-KinasesPhosphoproteinsPIK3CA protein, humanProtein Kinasesprotein kinase UPTK2 protein, humanReceptor-Interacting Protein Serine-Threonine Kinase 2Receptors, G-Protein-CoupledRIPK2 protein, humanSKP1 protein, humanS-Phase Kinase-Associated Proteinssrc-Family KinasesTP53 protein, humanTumor Suppressor Protein p53
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