Microscaled proteogenomic methods for precision oncology.

Biopsy, Large-Core Needle Breast Neoplasms / drug therapy Down-Regulation Humans Pilot Projects Proteogenomics / methods Receptor, ErbB-2 / genetics Signal Transduction TOR Serine-Threonine Kinases / genetics Trastuzumab / therapeutic use

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 Jan 2020
Historique:
received: 13 09 2019
accepted: 31 12 2019
entrez: 29 1 2020
pubmed: 29 1 2020
medline: 11 2 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-14381-2 PMID: 31988290 PMC: PMC6985126
pubmed: 31988290
doi: 10.1038/s41467-020-14381-2
pii: 10.1038/s41467-020-14381-2
pmc: PMC6985126
doi:

Substances chimiques

MTOR protein, human EC 2.7.1.1
ERBB2 protein, human EC 2.7.10.1
Receptor, ErbB-2 EC 2.7.10.1
TOR Serine-Threonine Kinases EC 2.7.11.1
Trastuzumab P188ANX8CK

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

532

Subventions

Organisme : NCI NIH HHS
ID : U24 CA210954
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA233223
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210986
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180860
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214125
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210979
Pays : United States

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Auteurs

Shankha Satpathy (S)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. shankha@broadinstitute.org.
ORCID: 0000-0002-6040-4854

Eric J Jaehnig (EJ)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0001-9618-6011

Karsten Krug (K)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.

Beom-Jun Kim (BJ)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Alexander B Saltzman (AB)

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.

Doug W Chan (DW)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Kimberly R Holloway (KR)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Meenakshi Anurag (M)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Chen Huang (C)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Purba Singh (P)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Ari Gao (A)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Noel Namai (N)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Yongchao Dou (Y)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Bo Wen (B)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0003-2261-3150

Suhas V Vasaikar (SV)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0001-9763-3899

David Mutch (D)

Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.

Mark A Watson (MA)

Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.

Cynthia Ma (C)

Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.

Foluso O Ademuyiwa (FO)

Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.

Mothaffar F Rimawi (MF)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0002-4284-5656

Rachel Schiff (R)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0003-1696-5213

Jeremy Hoog (J)

Siteman Comprehensive Cancer Center and Washington University School of Medicine, St. Louis, MO, 63110, USA.

Samuel Jacobs (S)

NSABP Foundation, Pittsburgh, PA, 15212, USA.

Anna Malovannaya (A)

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0003-2953-6485

Terry Hyslop (T)

Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA.

Karl R Clauser (KR)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.

D R Mani (DR)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.

Charles M Perou (CM)

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
ORCID: 0000-0001-9827-2247

George Miles (G)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.

Bing Zhang (B)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
ORCID: 0000-0001-8676-2425

Michael A Gillette (MA)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02115, USA.

Steven A Carr (SA)

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. scarr@broad.mit.edu.
ORCID: 0000-0002-7203-4299

Matthew J Ellis (MJ)

Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA. Matthew.Ellis@bcm.edu.
ORCID: 0000-0002-8467-8534

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytodiagnostic › Biopsie › Ponction-biopsie à l'aiguille › Biopsie au trocart › Microscaled proteogenomic methods for...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Microscaled proteogenomic methods for...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Microscaled proteogenomic methods for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Microscaled proteogenomic methods for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Projets pilotes › Microscaled proteogenomic methods for...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Protéogénomique › Microscaled proteogenomic methods for...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Récepteur ErbB-2 › Microscaled proteogenomic methods for...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Microscaled proteogenomic methods for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Microscaled proteogenomic methods for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Trastuzumab › Microscaled proteogenomic methods for...