Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11

AUTHORS

Paula Bernasconi-Elias, Tiancen Hu, David Jenkins, Brant Firestone, Sara Gans, Esther Kurth, Paola Capodieci, Joelle Deplazes-Lauber, Konstantin Petropoulos, Phillip Thiel, Dirk Ponsel, Sung Hee Choi, Peter LeMotte, Anne London, Margaret Goetcshkes, Erin Nolin, Michael D. Jones, Kelly Slocum, Michael J. Kluk, David M. Weinstock, Alexandra Christodoulou, Olga Weinberg, Jan Jaehrling, Seth A. Ettenberg, Alan Buckler, Stephen C. Blacklow, Jon C. Aster, Christy J. Fryer

ABSTRACT

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies. More... »

PAGES

6077-6086

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2016.133

DOI

http://dx.doi.org/10.1038/onc.2016.133

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028130316

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27157619


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Amino Acid Substitution", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibodies, Monoclonal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Codon", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Disease Models, Animal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epitopes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Precursor T-Cell Lymphoblastic Leukemia-Lymphoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Conformation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor, Notch3", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Xenograft Model Antitumor Assays", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bernasconi-Elias", 
        "givenName": "Paula", 
        "id": "sg:person.014655100335.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014655100335.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hu", 
        "givenName": "Tiancen", 
        "id": "sg:person.01046346123.80", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046346123.80"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jenkins", 
        "givenName": "David", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Firestone", 
        "givenName": "Brant", 
        "id": "sg:person.01034351441.05", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034351441.05"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gans", 
        "givenName": "Sara", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kurth", 
        "givenName": "Esther", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Capodieci", 
        "givenName": "Paola", 
        "id": "sg:person.0764750657.10", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764750657.10"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MorphoSys (Germany)", 
          "id": "https://www.grid.ac/institutes/grid.476513.2", 
          "name": [
            "MorphoSys AG, Martinsried, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Deplazes-Lauber", 
        "givenName": "Joelle", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MorphoSys (Germany)", 
          "id": "https://www.grid.ac/institutes/grid.476513.2", 
          "name": [
            "MorphoSys AG, Martinsried, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Petropoulos", 
        "givenName": "Konstantin", 
        "id": "sg:person.0727445313.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0727445313.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MorphoSys (Germany)", 
          "id": "https://www.grid.ac/institutes/grid.476513.2", 
          "name": [
            "MorphoSys AG, Martinsried, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Thiel", 
        "givenName": "Phillip", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MorphoSys (Germany)", 
          "id": "https://www.grid.ac/institutes/grid.476513.2", 
          "name": [
            "MorphoSys AG, Martinsried, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ponsel", 
        "givenName": "Dirk", 
        "id": "sg:person.0756415672.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756415672.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard University", 
          "id": "https://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Dana Farber Cancer Institute, Boston, MA", 
            "Harvard Medical School, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Choi", 
        "givenName": "Sung Hee", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "LeMotte", 
        "givenName": "Peter", 
        "id": "sg:person.01033457573.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033457573.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "London", 
        "givenName": "Anne", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Goetcshkes", 
        "givenName": "Margaret", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nolin", 
        "givenName": "Erin", 
        "id": "sg:person.011206044335.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011206044335.65"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jones", 
        "givenName": "Michael D.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Slocum", 
        "givenName": "Kelly", 
        "id": "sg:person.01240624130.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240624130.30"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brigham and Women's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.62560.37", 
          "name": [
            "Brigham and Women's Hospital, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kluk", 
        "givenName": "Michael J.", 
        "id": "sg:person.01330371370.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01330371370.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dana\u2013Farber Cancer Institute", 
          "id": "https://www.grid.ac/institutes/grid.65499.37", 
          "name": [
            "Dana Farber Cancer Institute, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Weinstock", 
        "givenName": "David M.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dana\u2013Farber Cancer Institute", 
          "id": "https://www.grid.ac/institutes/grid.65499.37", 
          "name": [
            "Dana Farber Cancer Institute, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Christodoulou", 
        "givenName": "Alexandra", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Children Hospital Boston, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Weinberg", 
        "givenName": "Olga", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MorphoSys (Germany)", 
          "id": "https://www.grid.ac/institutes/grid.476513.2", 
          "name": [
            "MorphoSys AG, Martinsried, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jaehrling", 
        "givenName": "Jan", 
        "id": "sg:person.01021772276.09", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021772276.09"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ettenberg", 
        "givenName": "Seth A.", 
        "id": "sg:person.01325640515.46", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01325640515.46"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Buckler", 
        "givenName": "Alan", 
        "id": "sg:person.0725766526.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725766526.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brigham and Women's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.62560.37", 
          "name": [
            "Dana Farber Cancer Institute, Boston, MA", 
            "Harvard Medical School, Boston, MA", 
            "Brigham and Women's Hospital, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Blacklow", 
        "givenName": "Stephen C.", 
        "id": "sg:person.014227025737.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014227025737.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Brigham and Women's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.62560.37", 
          "name": [
            "Harvard Medical School, Boston, MA", 
            "Brigham and Women's Hospital, Boston, MA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Aster", 
        "givenName": "Jon C.", 
        "id": "sg:person.01251567442.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01251567442.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Novartis (United States)", 
          "id": "https://www.grid.ac/institutes/grid.418424.f", 
          "name": [
            "Novartis Institutes for Biomedical Research, Cambridge, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fryer", 
        "givenName": "Christy J.", 
        "id": "sg:person.01034101751.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034101751.54"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/nature10166", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000736346", 
          "https://doi.org/10.1038/nature10166"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.22609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003340418"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003509222", 
          "https://doi.org/10.1038/nature02040"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003509222", 
          "https://doi.org/10.1038/nature02040"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.gastro.2011.06.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008148253"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.cir.0000160870.93058.dd", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009512692"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1242/dev.063610", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010560245"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.01655-05", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013198142"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0009094", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013347609"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsmb1227", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014955709", 
          "https://doi.org/10.1038/nsmb1227"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsmb1227", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014955709", 
          "https://doi.org/10.1038/nsmb1227"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature13146", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018681803", 
          "https://doi.org/10.1038/nature13146"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m800170200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019091386"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/emboj/19.13.3337", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019203918"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci35090", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020618401"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2009.03.045", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021056409"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt.1583", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022555745", 
          "https://doi.org/10.1038/nbt.1583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt.1583", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022555745", 
          "https://doi.org/10.1038/nbt.1583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.2643", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024397353", 
          "https://doi.org/10.1038/ng.2643"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08878", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026135489", 
          "https://doi.org/10.1038/nature08878"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08878", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026135489", 
          "https://doi.org/10.1038/nature08878"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m303164200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026341666"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2012.42.0992", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026977090"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/meth.2001.1262", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027621591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/meth.2001.1262", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027621591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-08-1564", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027942239"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-14-1348", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029399687"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg2484", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030687647", 
          "https://doi.org/10.1038/nrg2484"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jmb.2011.08.012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031386880"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.str.2015.05.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031453491"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2008-08-174748", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031533209"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/2159-8290.cd-13-0830", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033143973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1102160", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033243130"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.2580", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035286718", 
          "https://doi.org/10.1038/nm.2580"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jmb.2013.05.025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036004395"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature11003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036060000", 
          "https://doi.org/10.1038/nature11003"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0067306", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037604197"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.molcel.2004.10.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039358259"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsb1203-980", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040800493", 
          "https://doi.org/10.1038/nsb1203-980"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsb1203-980", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040800493", 
          "https://doi.org/10.1038/nsb1203-980"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.308904", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042025709"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35016111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042481749", 
          "https://doi.org/10.1038/35016111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35016111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042481749", 
          "https://doi.org/10.1038/35016111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg3272", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044688381", 
          "https://doi.org/10.1038/nrg3272"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci67201", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044831298"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/gene.10241", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044841881"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2014.02.018", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045220580"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc3035", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047048748", 
          "https://doi.org/10.1038/nrc3035"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-1597", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048883274"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0006613", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049350536"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074648217", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074752670", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2217/imt.09.23", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1078189025"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2016-11", 
    "datePublishedReg": "2016-11-01", 
    "description": "Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/onc.2016.133", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2475697", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2435834", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1097543", 
        "issn": [
          "0950-9232", 
          "1476-5594"
        ], 
        "name": "Oncogene", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "47", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "35"
      }
    ], 
    "name": "Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies", 
    "pagination": "6077-6086", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "8601a9c68552c145178ff085169a66a5c8f82b5c8a1f84eea434d94fd63e6989"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "27157619"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8711562"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/onc.2016.133"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1028130316"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/onc.2016.133", 
      "https://app.dimensions.ai/details/publication/pub.1028130316"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T19:15", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8678_00000550.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/onc/journal/v35/n47/full/onc2016133a.html"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/onc.2016.133'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/onc.2016.133'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/onc.2016.133'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/onc.2016.133'


 

This table displays all metadata directly associated to this object as RDF triples.

489 TRIPLES      21 PREDICATES      93 URIs      39 LITERALS      27 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/onc.2016.133 schema:about N3d162953dc3c4a7aad20bb2bac19ce78
2 N3e70208eb2174bd8b0c7b41cf6efc448
3 N4f360af584c647218c8eb093111565cb
4 N5345ad8da0024a9e92a7bb5e17f206c7
5 N5de2359b019e47fe80dd5249193e7cd9
6 N7192d07e6fc94e2284f5367ebda89b31
7 N7af8b187f1684bd0b84005ed5f5f1e66
8 N888fc10651ee416f8343422267a5f177
9 Na95abeb270674033836fd7e757ee2146
10 Nae86502bddad433a9757c4dde7cbd93c
11 Nc2f9fceeffb44da6afd41c1dc287e9f0
12 Nd90cb915e26447a8a2f8c09996dcb756
13 Ndb514a8caf7c4d3f983536f44f69b677
14 Nde720196eb0a45c887c01ae300fd8e9d
15 Ne3b60e7e20724ebcbd5aabf853cac641
16 Neb169f8ccfb74906b675374b1f467969
17 Neef4208695584570a48efc957314d47e
18 Nf125fc1397b2406e8394bdaaf0a2d247
19 anzsrc-for:11
20 anzsrc-for:1107
21 schema:author N1a3eacf74de141d693f7a123001e259f
22 schema:citation sg:pub.10.1038/35016111
23 sg:pub.10.1038/nature02040
24 sg:pub.10.1038/nature08878
25 sg:pub.10.1038/nature10166
26 sg:pub.10.1038/nature11003
27 sg:pub.10.1038/nature13146
28 sg:pub.10.1038/nbt.1583
29 sg:pub.10.1038/ng.2643
30 sg:pub.10.1038/nm.2580
31 sg:pub.10.1038/nrc3035
32 sg:pub.10.1038/nrg2484
33 sg:pub.10.1038/nrg3272
34 sg:pub.10.1038/nsb1203-980
35 sg:pub.10.1038/nsmb1227
36 https://app.dimensions.ai/details/publication/pub.1074648217
37 https://app.dimensions.ai/details/publication/pub.1074752670
38 https://doi.org/10.1002/gene.10241
39 https://doi.org/10.1002/ijc.22609
40 https://doi.org/10.1006/meth.2001.1262
41 https://doi.org/10.1016/j.ccr.2014.02.018
42 https://doi.org/10.1016/j.cell.2009.03.045
43 https://doi.org/10.1016/j.jmb.2011.08.012
44 https://doi.org/10.1016/j.jmb.2013.05.025
45 https://doi.org/10.1016/j.molcel.2004.10.014
46 https://doi.org/10.1016/j.str.2015.05.001
47 https://doi.org/10.1053/j.gastro.2011.06.003
48 https://doi.org/10.1074/jbc.m303164200
49 https://doi.org/10.1074/jbc.m800170200
50 https://doi.org/10.1093/emboj/19.13.3337
51 https://doi.org/10.1101/gad.308904
52 https://doi.org/10.1126/science.1102160
53 https://doi.org/10.1128/mcb.01655-05
54 https://doi.org/10.1158/0008-5472.can-07-1597
55 https://doi.org/10.1158/1078-0432.ccr-08-1564
56 https://doi.org/10.1158/1078-0432.ccr-14-1348
57 https://doi.org/10.1158/2159-8290.cd-13-0830
58 https://doi.org/10.1161/01.cir.0000160870.93058.dd
59 https://doi.org/10.1172/jci35090
60 https://doi.org/10.1172/jci67201
61 https://doi.org/10.1182/blood-2008-08-174748
62 https://doi.org/10.1200/jco.2012.42.0992
63 https://doi.org/10.1242/dev.063610
64 https://doi.org/10.1371/journal.pone.0006613
65 https://doi.org/10.1371/journal.pone.0009094
66 https://doi.org/10.1371/journal.pone.0067306
67 https://doi.org/10.2217/imt.09.23
68 schema:datePublished 2016-11
69 schema:datePublishedReg 2016-11-01
70 schema:description Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.
71 schema:genre research_article
72 schema:inLanguage en
73 schema:isAccessibleForFree true
74 schema:isPartOf N67067ec3c33e49d9b70e30c4858936a7
75 N8a8a47744390449680750ae8018d008b
76 sg:journal.1097543
77 schema:name Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies
78 schema:pagination 6077-6086
79 schema:productId N13ca3b10f61a4319a0b7eb0a6109c5d5
80 N5140e3594150432d928767e96596671b
81 N648c2ff099354a648e10eea433335d38
82 Nb37b5ed1c9724c6dbda5e24749279c02
83 Nb3cccbb8fc964f889be8ab09cf438da0
84 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028130316
85 https://doi.org/10.1038/onc.2016.133
86 schema:sdDatePublished 2019-04-10T19:15
87 schema:sdLicense https://scigraph.springernature.com/explorer/license/
88 schema:sdPublisher Nb01450563de04e4d9838d7d4527e9587
89 schema:url http://www.nature.com/onc/journal/v35/n47/full/onc2016133a.html
90 sgo:license sg:explorer/license/
91 sgo:sdDataset articles
92 rdf:type schema:ScholarlyArticle
93 N098b4062202d438eb26c08a167dbf7c0 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
94 schema:familyName Gans
95 schema:givenName Sara
96 rdf:type schema:Person
97 N13ca3b10f61a4319a0b7eb0a6109c5d5 schema:name pubmed_id
98 schema:value 27157619
99 rdf:type schema:PropertyValue
100 N1a3eacf74de141d693f7a123001e259f rdf:first sg:person.014655100335.37
101 rdf:rest Nc26d697315cf4de59e79b8bcda77ec57
102 N2a9835bb7add4608a8d89c9da8b79b55 rdf:first sg:person.014227025737.12
103 rdf:rest N6b75a66595bb4e8e9092d16e072660cb
104 N2e2926c2674e4b3098ff73c4f0044092 rdf:first sg:person.0764750657.10
105 rdf:rest N9e22af890a964257a0f61586de122a8e
106 N3d162953dc3c4a7aad20bb2bac19ce78 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Xenograft Model Antitumor Assays
108 rdf:type schema:DefinedTerm
109 N3e70208eb2174bd8b0c7b41cf6efc448 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Antineoplastic Agents
111 rdf:type schema:DefinedTerm
112 N4ef9ba4d151b4c6fac2f3eb67c28d9f4 rdf:first Nb645bed29b8f4dd0a812ef90533a3953
113 rdf:rest Ne7ad73b3573847c6ab613c7467e3e596
114 N4f360af584c647218c8eb093111565cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Animals
116 rdf:type schema:DefinedTerm
117 N5140e3594150432d928767e96596671b schema:name doi
118 schema:value 10.1038/onc.2016.133
119 rdf:type schema:PropertyValue
120 N5345ad8da0024a9e92a7bb5e17f206c7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
121 schema:name Codon
122 rdf:type schema:DefinedTerm
123 N571846f755d14ad0bdb831e949028591 rdf:first sg:person.011206044335.65
124 rdf:rest N80f67f35d0c141c5b9e775ba3d09daa2
125 N589dbb62d595494bac7ee2b0b7b04e69 rdf:first Ndbbd12ee976841f2a17263db6a736489
126 rdf:rest Nb95fa6ae5d9c4dd7b41c9074a4e284f7
127 N5de2359b019e47fe80dd5249193e7cd9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Female
129 rdf:type schema:DefinedTerm
130 N60c5c9723dad4e0fb65a44197ca35f8c schema:affiliation Ne4589ff3def24596ae3595df2f743d5a
131 schema:familyName Weinberg
132 schema:givenName Olga
133 rdf:type schema:Person
134 N648c2ff099354a648e10eea433335d38 schema:name readcube_id
135 schema:value 8601a9c68552c145178ff085169a66a5c8f82b5c8a1f84eea434d94fd63e6989
136 rdf:type schema:PropertyValue
137 N67067ec3c33e49d9b70e30c4858936a7 schema:issueNumber 47
138 rdf:type schema:PublicationIssue
139 N6b75a66595bb4e8e9092d16e072660cb rdf:first sg:person.01251567442.27
140 rdf:rest N8fc6e77bf7714966af6a0abb22bd3b6d
141 N6bb04f3f5a024f099a6abf4a131756ea schema:affiliation https://www.grid.ac/institutes/grid.65499.37
142 schema:familyName Weinstock
143 schema:givenName David M.
144 rdf:type schema:Person
145 N6ca2956e0d1146f9b616ebecb9ca8355 rdf:first N098b4062202d438eb26c08a167dbf7c0
146 rdf:rest Nc0e5c073b05f401fbacbedf37f0c0305
147 N7192d07e6fc94e2284f5367ebda89b31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Receptor, Notch3
149 rdf:type schema:DefinedTerm
150 N71b9b46b58f54e7eb6715ce34b3de93f rdf:first Nbb7f4efa27ad49578b1cd7404081cfef
151 rdf:rest N571846f755d14ad0bdb831e949028591
152 N77d4f879076f4056a91270c562370500 rdf:first Nca8572b953714a4da40a325918d44f24
153 rdf:rest N71b9b46b58f54e7eb6715ce34b3de93f
154 N7af8b187f1684bd0b84005ed5f5f1e66 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
155 schema:name Humans
156 rdf:type schema:DefinedTerm
157 N7da9ac5f6ca84f12b90e5572909d5495 rdf:first Ne6fe52af40ec423cb2162f1da31358f2
158 rdf:rest Ne52d0dee904c4293b44c90235b1cde33
159 N80f67f35d0c141c5b9e775ba3d09daa2 rdf:first Nd8f37ba046e64733bdbc98336259f98f
160 rdf:rest N91e0e299ef9947d988f1a188335136de
161 N888fc10651ee416f8343422267a5f177 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Mutation
163 rdf:type schema:DefinedTerm
164 N8a8a47744390449680750ae8018d008b schema:volumeNumber 35
165 rdf:type schema:PublicationVolume
166 N8fc6e77bf7714966af6a0abb22bd3b6d rdf:first sg:person.01034101751.54
167 rdf:rest rdf:nil
168 N91e0e299ef9947d988f1a188335136de rdf:first sg:person.01240624130.30
169 rdf:rest Nf906be5c7c504e53b75b426a5eda3af1
170 N9e22af890a964257a0f61586de122a8e rdf:first Nfad6b4ba9f07416282bdc8921bb9e4db
171 rdf:rest Nbd17884c4f5f4fe3b0c2a99d35038c07
172 N9f44e20cf2db43bea7ce7b7b12865fb0 rdf:first sg:person.01325640515.46
173 rdf:rest Nc2df9090b1d84ee99afd5be31f9bb1c3
174 Na4a269ca495d4592a10b96771c756ca7 rdf:first Ncdd659e62ca146c3bf74c3d99c79a2eb
175 rdf:rest Nd3d2fb3de33543ccb7d5c358330ce99e
176 Na95abeb270674033836fd7e757ee2146 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Protein Conformation
178 rdf:type schema:DefinedTerm
179 Nae86502bddad433a9757c4dde7cbd93c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
180 schema:name Models, Molecular
181 rdf:type schema:DefinedTerm
182 Nb01450563de04e4d9838d7d4527e9587 schema:name Springer Nature - SN SciGraph project
183 rdf:type schema:Organization
184 Nb37b5ed1c9724c6dbda5e24749279c02 schema:name dimensions_id
185 schema:value pub.1028130316
186 rdf:type schema:PropertyValue
187 Nb3cccbb8fc964f889be8ab09cf438da0 schema:name nlm_unique_id
188 schema:value 8711562
189 rdf:type schema:PropertyValue
190 Nb645bed29b8f4dd0a812ef90533a3953 schema:affiliation https://www.grid.ac/institutes/grid.65499.37
191 schema:familyName Christodoulou
192 schema:givenName Alexandra
193 rdf:type schema:Person
194 Nb95fa6ae5d9c4dd7b41c9074a4e284f7 rdf:first sg:person.01033457573.90
195 rdf:rest N77d4f879076f4056a91270c562370500
196 Nbb76d14f2a5a4adb928d1b456c953fe9 rdf:first sg:person.01021772276.09
197 rdf:rest N9f44e20cf2db43bea7ce7b7b12865fb0
198 Nbb7f4efa27ad49578b1cd7404081cfef schema:affiliation https://www.grid.ac/institutes/grid.418424.f
199 schema:familyName Goetcshkes
200 schema:givenName Margaret
201 rdf:type schema:Person
202 Nbd17884c4f5f4fe3b0c2a99d35038c07 rdf:first sg:person.0727445313.31
203 rdf:rest Na4a269ca495d4592a10b96771c756ca7
204 Nbdcd62d6d1f248b88247262dbc1a8b9f schema:affiliation https://www.grid.ac/institutes/grid.418424.f
205 schema:familyName Kurth
206 schema:givenName Esther
207 rdf:type schema:Person
208 Nc0e5c073b05f401fbacbedf37f0c0305 rdf:first Nbdcd62d6d1f248b88247262dbc1a8b9f
209 rdf:rest N2e2926c2674e4b3098ff73c4f0044092
210 Nc26d697315cf4de59e79b8bcda77ec57 rdf:first sg:person.01046346123.80
211 rdf:rest N7da9ac5f6ca84f12b90e5572909d5495
212 Nc2df9090b1d84ee99afd5be31f9bb1c3 rdf:first sg:person.0725766526.54
213 rdf:rest N2a9835bb7add4608a8d89c9da8b79b55
214 Nc2f9fceeffb44da6afd41c1dc287e9f0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
215 schema:name Mice
216 rdf:type schema:DefinedTerm
217 Nc481edb0d53b410dae431e8c0182a3a0 rdf:first N6bb04f3f5a024f099a6abf4a131756ea
218 rdf:rest N4ef9ba4d151b4c6fac2f3eb67c28d9f4
219 Nca8572b953714a4da40a325918d44f24 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
220 schema:familyName London
221 schema:givenName Anne
222 rdf:type schema:Person
223 Ncdd659e62ca146c3bf74c3d99c79a2eb schema:affiliation https://www.grid.ac/institutes/grid.476513.2
224 schema:familyName Thiel
225 schema:givenName Phillip
226 rdf:type schema:Person
227 Nd3d2fb3de33543ccb7d5c358330ce99e rdf:first sg:person.0756415672.16
228 rdf:rest N589dbb62d595494bac7ee2b0b7b04e69
229 Nd8f37ba046e64733bdbc98336259f98f schema:affiliation https://www.grid.ac/institutes/grid.418424.f
230 schema:familyName Jones
231 schema:givenName Michael D.
232 rdf:type schema:Person
233 Nd90cb915e26447a8a2f8c09996dcb756 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
234 schema:name Antibodies, Monoclonal
235 rdf:type schema:DefinedTerm
236 Ndb514a8caf7c4d3f983536f44f69b677 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
237 schema:name Amino Acid Substitution
238 rdf:type schema:DefinedTerm
239 Ndbbd12ee976841f2a17263db6a736489 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
240 schema:familyName Choi
241 schema:givenName Sung Hee
242 rdf:type schema:Person
243 Nde720196eb0a45c887c01ae300fd8e9d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
244 schema:name Disease Models, Animal
245 rdf:type schema:DefinedTerm
246 Ne3b60e7e20724ebcbd5aabf853cac641 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
247 schema:name Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
248 rdf:type schema:DefinedTerm
249 Ne4589ff3def24596ae3595df2f743d5a schema:name Children Hospital Boston, Boston, MA
250 rdf:type schema:Organization
251 Ne52d0dee904c4293b44c90235b1cde33 rdf:first sg:person.01034351441.05
252 rdf:rest N6ca2956e0d1146f9b616ebecb9ca8355
253 Ne6fe52af40ec423cb2162f1da31358f2 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
254 schema:familyName Jenkins
255 schema:givenName David
256 rdf:type schema:Person
257 Ne7ad73b3573847c6ab613c7467e3e596 rdf:first N60c5c9723dad4e0fb65a44197ca35f8c
258 rdf:rest Nbb76d14f2a5a4adb928d1b456c953fe9
259 Neb169f8ccfb74906b675374b1f467969 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
260 schema:name Epitopes
261 rdf:type schema:DefinedTerm
262 Neef4208695584570a48efc957314d47e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
263 schema:name Cell Line, Tumor
264 rdf:type schema:DefinedTerm
265 Nf125fc1397b2406e8394bdaaf0a2d247 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
266 schema:name Signal Transduction
267 rdf:type schema:DefinedTerm
268 Nf906be5c7c504e53b75b426a5eda3af1 rdf:first sg:person.01330371370.54
269 rdf:rest Nc481edb0d53b410dae431e8c0182a3a0
270 Nfad6b4ba9f07416282bdc8921bb9e4db schema:affiliation https://www.grid.ac/institutes/grid.476513.2
271 schema:familyName Deplazes-Lauber
272 schema:givenName Joelle
273 rdf:type schema:Person
274 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
275 schema:name Medical and Health Sciences
276 rdf:type schema:DefinedTerm
277 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
278 schema:name Immunology
279 rdf:type schema:DefinedTerm
280 sg:grant.2435834 http://pending.schema.org/fundedItem sg:pub.10.1038/onc.2016.133
281 rdf:type schema:MonetaryGrant
282 sg:grant.2475697 http://pending.schema.org/fundedItem sg:pub.10.1038/onc.2016.133
283 rdf:type schema:MonetaryGrant
284 sg:journal.1097543 schema:issn 0950-9232
285 1476-5594
286 schema:name Oncogene
287 rdf:type schema:Periodical
288 sg:person.01021772276.09 schema:affiliation https://www.grid.ac/institutes/grid.476513.2
289 schema:familyName Jaehrling
290 schema:givenName Jan
291 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021772276.09
292 rdf:type schema:Person
293 sg:person.01033457573.90 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
294 schema:familyName LeMotte
295 schema:givenName Peter
296 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033457573.90
297 rdf:type schema:Person
298 sg:person.01034101751.54 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
299 schema:familyName Fryer
300 schema:givenName Christy J.
301 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034101751.54
302 rdf:type schema:Person
303 sg:person.01034351441.05 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
304 schema:familyName Firestone
305 schema:givenName Brant
306 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01034351441.05
307 rdf:type schema:Person
308 sg:person.01046346123.80 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
309 schema:familyName Hu
310 schema:givenName Tiancen
311 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046346123.80
312 rdf:type schema:Person
313 sg:person.011206044335.65 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
314 schema:familyName Nolin
315 schema:givenName Erin
316 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011206044335.65
317 rdf:type schema:Person
318 sg:person.01240624130.30 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
319 schema:familyName Slocum
320 schema:givenName Kelly
321 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240624130.30
322 rdf:type schema:Person
323 sg:person.01251567442.27 schema:affiliation https://www.grid.ac/institutes/grid.62560.37
324 schema:familyName Aster
325 schema:givenName Jon C.
326 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01251567442.27
327 rdf:type schema:Person
328 sg:person.01325640515.46 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
329 schema:familyName Ettenberg
330 schema:givenName Seth A.
331 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01325640515.46
332 rdf:type schema:Person
333 sg:person.01330371370.54 schema:affiliation https://www.grid.ac/institutes/grid.62560.37
334 schema:familyName Kluk
335 schema:givenName Michael J.
336 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01330371370.54
337 rdf:type schema:Person
338 sg:person.014227025737.12 schema:affiliation https://www.grid.ac/institutes/grid.62560.37
339 schema:familyName Blacklow
340 schema:givenName Stephen C.
341 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014227025737.12
342 rdf:type schema:Person
343 sg:person.014655100335.37 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
344 schema:familyName Bernasconi-Elias
345 schema:givenName Paula
346 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014655100335.37
347 rdf:type schema:Person
348 sg:person.0725766526.54 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
349 schema:familyName Buckler
350 schema:givenName Alan
351 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725766526.54
352 rdf:type schema:Person
353 sg:person.0727445313.31 schema:affiliation https://www.grid.ac/institutes/grid.476513.2
354 schema:familyName Petropoulos
355 schema:givenName Konstantin
356 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0727445313.31
357 rdf:type schema:Person
358 sg:person.0756415672.16 schema:affiliation https://www.grid.ac/institutes/grid.476513.2
359 schema:familyName Ponsel
360 schema:givenName Dirk
361 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756415672.16
362 rdf:type schema:Person
363 sg:person.0764750657.10 schema:affiliation https://www.grid.ac/institutes/grid.418424.f
364 schema:familyName Capodieci
365 schema:givenName Paola
366 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0764750657.10
367 rdf:type schema:Person
368 sg:pub.10.1038/35016111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042481749
369 https://doi.org/10.1038/35016111
370 rdf:type schema:CreativeWork
371 sg:pub.10.1038/nature02040 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003509222
372 https://doi.org/10.1038/nature02040
373 rdf:type schema:CreativeWork
374 sg:pub.10.1038/nature08878 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026135489
375 https://doi.org/10.1038/nature08878
376 rdf:type schema:CreativeWork
377 sg:pub.10.1038/nature10166 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000736346
378 https://doi.org/10.1038/nature10166
379 rdf:type schema:CreativeWork
380 sg:pub.10.1038/nature11003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036060000
381 https://doi.org/10.1038/nature11003
382 rdf:type schema:CreativeWork
383 sg:pub.10.1038/nature13146 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018681803
384 https://doi.org/10.1038/nature13146
385 rdf:type schema:CreativeWork
386 sg:pub.10.1038/nbt.1583 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022555745
387 https://doi.org/10.1038/nbt.1583
388 rdf:type schema:CreativeWork
389 sg:pub.10.1038/ng.2643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024397353
390 https://doi.org/10.1038/ng.2643
391 rdf:type schema:CreativeWork
392 sg:pub.10.1038/nm.2580 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035286718
393 https://doi.org/10.1038/nm.2580
394 rdf:type schema:CreativeWork
395 sg:pub.10.1038/nrc3035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047048748
396 https://doi.org/10.1038/nrc3035
397 rdf:type schema:CreativeWork
398 sg:pub.10.1038/nrg2484 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030687647
399 https://doi.org/10.1038/nrg2484
400 rdf:type schema:CreativeWork
401 sg:pub.10.1038/nrg3272 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044688381
402 https://doi.org/10.1038/nrg3272
403 rdf:type schema:CreativeWork
404 sg:pub.10.1038/nsb1203-980 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040800493
405 https://doi.org/10.1038/nsb1203-980
406 rdf:type schema:CreativeWork
407 sg:pub.10.1038/nsmb1227 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014955709
408 https://doi.org/10.1038/nsmb1227
409 rdf:type schema:CreativeWork
410 https://app.dimensions.ai/details/publication/pub.1074648217 schema:CreativeWork
411 https://app.dimensions.ai/details/publication/pub.1074752670 schema:CreativeWork
412 https://doi.org/10.1002/gene.10241 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044841881
413 rdf:type schema:CreativeWork
414 https://doi.org/10.1002/ijc.22609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003340418
415 rdf:type schema:CreativeWork
416 https://doi.org/10.1006/meth.2001.1262 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027621591
417 rdf:type schema:CreativeWork
418 https://doi.org/10.1016/j.ccr.2014.02.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045220580
419 rdf:type schema:CreativeWork
420 https://doi.org/10.1016/j.cell.2009.03.045 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021056409
421 rdf:type schema:CreativeWork
422 https://doi.org/10.1016/j.jmb.2011.08.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031386880
423 rdf:type schema:CreativeWork
424 https://doi.org/10.1016/j.jmb.2013.05.025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036004395
425 rdf:type schema:CreativeWork
426 https://doi.org/10.1016/j.molcel.2004.10.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039358259
427 rdf:type schema:CreativeWork
428 https://doi.org/10.1016/j.str.2015.05.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031453491
429 rdf:type schema:CreativeWork
430 https://doi.org/10.1053/j.gastro.2011.06.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008148253
431 rdf:type schema:CreativeWork
432 https://doi.org/10.1074/jbc.m303164200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026341666
433 rdf:type schema:CreativeWork
434 https://doi.org/10.1074/jbc.m800170200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019091386
435 rdf:type schema:CreativeWork
436 https://doi.org/10.1093/emboj/19.13.3337 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019203918
437 rdf:type schema:CreativeWork
438 https://doi.org/10.1101/gad.308904 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042025709
439 rdf:type schema:CreativeWork
440 https://doi.org/10.1126/science.1102160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033243130
441 rdf:type schema:CreativeWork
442 https://doi.org/10.1128/mcb.01655-05 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013198142
443 rdf:type schema:CreativeWork
444 https://doi.org/10.1158/0008-5472.can-07-1597 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048883274
445 rdf:type schema:CreativeWork
446 https://doi.org/10.1158/1078-0432.ccr-08-1564 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027942239
447 rdf:type schema:CreativeWork
448 https://doi.org/10.1158/1078-0432.ccr-14-1348 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029399687
449 rdf:type schema:CreativeWork
450 https://doi.org/10.1158/2159-8290.cd-13-0830 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033143973
451 rdf:type schema:CreativeWork
452 https://doi.org/10.1161/01.cir.0000160870.93058.dd schema:sameAs https://app.dimensions.ai/details/publication/pub.1009512692
453 rdf:type schema:CreativeWork
454 https://doi.org/10.1172/jci35090 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020618401
455 rdf:type schema:CreativeWork
456 https://doi.org/10.1172/jci67201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044831298
457 rdf:type schema:CreativeWork
458 https://doi.org/10.1182/blood-2008-08-174748 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031533209
459 rdf:type schema:CreativeWork
460 https://doi.org/10.1200/jco.2012.42.0992 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026977090
461 rdf:type schema:CreativeWork
462 https://doi.org/10.1242/dev.063610 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010560245
463 rdf:type schema:CreativeWork
464 https://doi.org/10.1371/journal.pone.0006613 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049350536
465 rdf:type schema:CreativeWork
466 https://doi.org/10.1371/journal.pone.0009094 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013347609
467 rdf:type schema:CreativeWork
468 https://doi.org/10.1371/journal.pone.0067306 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037604197
469 rdf:type schema:CreativeWork
470 https://doi.org/10.2217/imt.09.23 schema:sameAs https://app.dimensions.ai/details/publication/pub.1078189025
471 rdf:type schema:CreativeWork
472 https://www.grid.ac/institutes/grid.38142.3c schema:alternateName Harvard University
473 schema:name Dana Farber Cancer Institute, Boston, MA
474 Harvard Medical School, Boston, MA
475 rdf:type schema:Organization
476 https://www.grid.ac/institutes/grid.418424.f schema:alternateName Novartis (United States)
477 schema:name Novartis Institutes for Biomedical Research, Cambridge, Massachusetts
478 rdf:type schema:Organization
479 https://www.grid.ac/institutes/grid.476513.2 schema:alternateName MorphoSys (Germany)
480 schema:name MorphoSys AG, Martinsried, Germany
481 rdf:type schema:Organization
482 https://www.grid.ac/institutes/grid.62560.37 schema:alternateName Brigham and Women's Hospital
483 schema:name Brigham and Women's Hospital, Boston, MA
484 Dana Farber Cancer Institute, Boston, MA
485 Harvard Medical School, Boston, MA
486 rdf:type schema:Organization
487 https://www.grid.ac/institutes/grid.65499.37 schema:alternateName Dana–Farber Cancer Institute
488 schema:name Dana Farber Cancer Institute, Boston, MA
489 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...