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Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.
Krug, Karsten; Jaehnig, Eric J; Satpathy, Shankha; Blumenberg, Lili; Karpova, Alla; Anurag, Meenakshi; Miles, George; Mertins, Philipp; Geffen, Yifat; Tang, Lauren C; Heiman, David I; Cao, Song; Maruvka, Yosef E; Lei, Jonathan T; Huang, Chen; Kothadia, Ramani B; Colaprico, Antonio; Birger, Chet; Wang, Jarey; Dou, Yongchao; Wen, Bo; Shi, Zhiao; Liao, Yuxing; Wiznerowicz, Maciej; Wyczalkowski, Matthew A; Chen, Xi Steven; Kennedy, Jacob J; Paulovich, Amanda G; Thiagarajan, Mathangi; Kinsinger, Christopher R; Hiltke, Tara; Boja, Emily S; Mesri, Mehdi; Robles, Ana I; Rodriguez, Henry; Westbrook, Thomas F; Ding, Li; Getz, Gad; Clauser, Karl R; Fenyö, David; Ruggles, Kelly V; Zhang, Bing; Mani, D R; Carr, Steven A; Ellis, Matthew J; Gillette, Michael A.
Afiliación
  • Krug K; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Jaehnig EJ; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Satpathy S; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Blumenberg L; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Karpova A; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Anurag M; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Miles G; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mertins P; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Max Delbrück Center for Molecular Medicine in the Helmholtz Society and Berlin Institute of Health, Berlin, Germany.
  • Geffen Y; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, 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.
  • Heiman DI; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Cao S; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Maruvka YE; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Lei JT; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Huang C; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Kothadia RB; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Colaprico A; Division of Biostatistics, Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Birger C; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Wang J; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Dou Y; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wen B; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shi Z; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liao Y; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wiznerowicz M; Poznan University of Medical Sciences, Poznan 61-701, Poland; International Institute for Molecular Oncology, 60-203 Poznan, Poland.
  • Wyczalkowski MA; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Chen XS; Division of Biostatistics, Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
  • Kennedy JJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Paulovich AG; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Thiagarajan M; Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Kinsinger CR; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Hiltke T; 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.
  • Mesri M; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Rodriguez H; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Westbrook TF; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Ding L; Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Getz G; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02114, USA.
  • Clauser KR; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  • Fenyö D; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Ruggles KV; Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Zhang B; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mani DR; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: manidr@broadinstitute.org.
  • Carr SA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: scarr@broad.mit.edu.
  • Ellis MJ; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mjellis@bcm.edu.
  • 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 02114, USA. Electronic address: gillette@broadinstitute.org.
Cell ; 183(5): 1436-1456.e31, 2020 11 25.
Article en En | MEDLINE | ID: mdl-33212010
ABSTRACT
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Terapia Molecular Dirigida / Carcinogénesis / Proteogenómica Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Terapia Molecular Dirigida / Carcinogénesis / Proteogenómica Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos