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Microscaled proteogenomic methods for precision oncology.
Satpathy, Shankha; Jaehnig, Eric J; Krug, Karsten; Kim, Beom-Jun; Saltzman, Alexander B; Chan, Doug W; Holloway, Kimberly R; Anurag, Meenakshi; Huang, Chen; Singh, Purba; Gao, Ari; Namai, Noel; Dou, Yongchao; Wen, Bo; Vasaikar, Suhas V; Mutch, David; Watson, Mark A; Ma, Cynthia; Ademuyiwa, Foluso O; Rimawi, Mothaffar F; Schiff, Rachel; Hoog, Jeremy; Jacobs, Samuel; Malovannaya, Anna; Hyslop, Terry; Clauser, Karl R; Mani, D R; Perou, Charles M; Miles, George; Zhang, Bing; Gillette, Michael A; Carr, Steven A; Ellis, Matthew J.
Afiliación
  • Satpathy S; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. shankha@broadinstitute.org.
  • Jaehnig EJ; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Krug K; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
  • Kim BJ; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Saltzman AB; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Chan DW; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Holloway KR; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Anurag M; 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.
  • Singh P; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Gao A; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Namai N; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer 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.
  • Vasaikar SV; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Mutch D; Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Watson MA; Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Ma C; Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Ademuyiwa FO; Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Rimawi MF; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Schiff R; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Hoog J; Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Jacobs S; NSABP Foundation, Pittsburgh, PA, 15212, USA.
  • Malovannaya A; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Hyslop T; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA.
  • Clauser KR; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
  • Mani DR; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
  • Perou CM; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
  • Miles G; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Zhang B; Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Gillette MA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
  • Carr SA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02115, USA.
  • Ellis MJ; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. scarr@broad.mit.edu.
Nat Commun ; 11(1): 532, 2020 Jan 27.
Article en En | MEDLINE | ID: mdl-31988290
Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptor ErbB-2 / Trastuzumab / Proteogenómica Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptor ErbB-2 / Trastuzumab / Proteogenómica Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido