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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.","is_dataset_classified":null,"base_score":7.48324441607385,"endowment":7.48324441607385,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27251275","pmcid":"PMC5102256","openalex_id":"https://openalex.org/W2395887422","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"P41 GM103422","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U24 CA160034","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA091842","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U24 CA159988","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U24CA160019","title":null},{"funder_name":"NIGMS NIH 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Proteome Characterization Center"},{"funder_name":"National Institutes of Health","grant_id":"5U24CA160019-03","title":"Center for Application of Advanced Clinical Proteomic Technologies for Cancer"},{"funder_name":"National Institutes of Health","grant_id":"5U24CA160035-03","title":"Cancer Proteome Center at Washington Univ, Univ of North Carolina"},{"funder_name":"National Institutes of Health","grant_id":"5R01GM108711-05","title":"Integrative multivariate association and genomic analyses"},{"funder_name":"National Institutes of Health","grant_id":"5U24CA160036-02","title":"Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers"},{"funder_name":"National Institutes of Health","grant_id":"5U24CA160034-02","title":"Proteo-genomic Discovery, Prioritization and Verification of Cancer Biomarkers"},{"funder_name":"National Institutes of Health","grant_id":"5P30CA091842-05","title":"Core--Pharmacology Facility"}],"total_grants":24,"fwci":68.1728,"citation_percentile":0.99980779,"influential_citations":59,"citation_trend":[{"year":2016,"count":42},{"year":2017,"count":149},{"year":2018,"count":197},{"year":2019,"count":190},{"year":2020,"count":233},{"year":2021,"count":261},{"year":2022,"count":208},{"year":2023,"count":159},{"year":2024,"count":140},{"year":2025,"count":125},{"year":2026,"count":69}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626102","host_type":"repository"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626102","host_type":"GREEN"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626102","host_type":"repository"},{"url":"http://www.nature.com/articles/nature18003.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/nature18003","host_type":"publisher"},{"url":"https://doi.org/10.1038/nature18003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27251275","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5102256","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5102256","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5102256?pdf=render","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/pmc5102256?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.17615/mepw-5x28","host_type":""},{"url":"http://dx.doi.org/10.1038/nature18003","host_type":""},{"url":"https://dx.doi.org/10.1038/nature18003","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/nature18003","host_type":""}],"fields_of_study":["Cancer Genomics and Diagnostics","Breast Cancer Treatment Studies","Cancer-related Molecular Pathways","Medicine","Biology","0301 basic medicine","03 medical and health sciences","0303 health sciences","Breast Neoplasms","Calcium-Binding Proteins","Chromosome Deletion","Chromosomes, Human, Pair 5","Class I Phosphatidylinositol 3-Kinases","Cyclin-Dependent Kinases","ErbB Receptors","Female","Focal Adhesion Kinase 1","Gene Expression Regulation, Neoplastic","Genomics","Humans","Mass Spectrometry","Molecular Sequence Annotation","Mutation","Phosphatidylinositol 3-Kinases","Phosphoproteins","Protein Kinases","Proteomics","Erb-b2 Receptor Tyrosine Kinases","Receptor-Interacting Protein Serine-Threonine Kinase 2","Receptors, G-Protein-Coupled","S-Phase Kinase-Associated Proteins","Signal Transduction","Tumor Suppressor Protein p53","p21-Activated Kinases","src-Family Kinases"],"mesh_terms":["Breast Neoplasms","Calcium-Binding Proteins","Chromosome Deletion","Chromosomes, Human, Pair 5","Female","Humans","Mutation","Phosphoproteins","Protein Kinases","Mass Spectrometry","Signal Transduction","Gene Expression Regulation, Neoplastic","Tumor Suppressor Protein p53","Erb-b2 Receptor Tyrosine Kinases","Receptor, ErbB-2","Cyclin-Dependent Kinases","src-Family Kinases","Phosphatidylinositol 3-Kinases","Genomics","Proteomics","Receptors, G-Protein-Coupled","S-Phase Kinase-Associated Proteins","Focal Adhesion Kinase 1","Receptor-Interacting Protein Serine-Threonine Kinase 2","p21-Activated Kinases","Class I Phosphatidylinositol 3-Kinases","Molecular Sequence Annotation","ErbB Receptors"],"keywords":["Proteogenomics","Somatic cell","Breast cancer","Biology","Germline mutation","Signalling","Genetics","Mutation","Cancer","Computational biology","Cancer research","Genome","Genomics","Gene","Cell biology","Proteomics","Class I Phosphatidylinositol 3-Kinases","610","Breast Neoplasms","Erb-b2 Receptor Tyrosine Kinases","Article","Mass Spectrometry","Phosphatidylinositol 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