Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-05-20

AUTHORS

Andrew Woolston, Louise J. Barber, Beatrice Griffiths, Oriol Pich, Nuria Lopez-Bigas, Nik Matthews, Sheela Rao, David Watkins, Ian Chau, Naureen Starling, David Cunningham, Marco Gerlinger

ABSTRACT

Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor. More... »

PAGES

1024-1032

References to SciGraph publications

  • 2020-02-05. The repertoire of mutational signatures in human cancer in NATURE
  • 2015-11-09. Clock-like mutational processes in human somatic cells in NATURE GENETICS
  • 2016-02-22. deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution in GENOME BIOLOGY
  • 2018-09-10. Mutational signature distribution varies with DNA replication timing and strand asymmetry in GENOME BIOLOGY
  • 2010-09-28. How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine in BRITISH JOURNAL OF CANCER
  • 2018-04-25. MutationalPatterns: comprehensive genome-wide analysis of mutational processes in GENOME MEDICINE
  • 2012-06-13. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers in NATURE
  • 2012-06-13. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer in NATURE
  • 2019-09-02. SigsPack, a package for cancer mutational signatures in BMC BIOINFORMATICS
  • 2012-01-22. Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer in NATURE MEDICINE
  • 2017-06-08. Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance in NATURE COMMUNICATIONS
  • 2013-09-26. The Cancer Genome Atlas Pan-Cancer analysis project in NATURE GENETICS
  • 2019-11-18. The mutational footprints of cancer therapies in NATURE GENETICS
  • 2017-05-24. Multilevel genomics of colorectal cancers with microsatellite instability—clinical impact of JAK1 mutations and consensus molecular subtype 1 in GENOME MEDICINE
  • 2020-02-05. The evolutionary history of 2,658 cancers in NATURE
  • 2019-10-08. 5-Fluorouracil treatment induces characteristic T>G mutations in human cancer in NATURE COMMUNICATIONS
  • 2019-10-23. Pan-cancer whole-genome analyses of metastatic solid tumours in NATURE
  • 2018-05-10. The effects of mutational processes and selection on driver mutations across cancer types in NATURE COMMUNICATIONS
  • 2013-08-14. Signatures of mutational processes in human cancer in NATURE
  • 2019-04-18. decompTumor2Sig: identification of mutational signatures active in individual tumors in BMC BIOINFORMATICS
  • 2019-07-05. A practical guide for mutational signature analysis in hematological malignancies in NATURE COMMUNICATIONS
  • 2017-09-15. Classifying the evolutionary and ecological features of neoplasms in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41559-021-01470-8

    DOI

    http://dx.doi.org/10.1038/s41559-021-01470-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1138201806

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34017094


    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/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antineoplastic Agents, Immunological", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cetuximab", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Colorectal Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.18886.3f", 
              "name": [
                "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Woolston", 
            "givenName": "Andrew", 
            "id": "sg:person.01145246415.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01145246415.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.18886.3f", 
              "name": [
                "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Barber", 
            "givenName": "Louise J.", 
            "id": "sg:person.01231216510.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01231216510.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.18886.3f", 
              "name": [
                "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Griffiths", 
            "givenName": "Beatrice", 
            "id": "sg:person.010411247077.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010411247077.27"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain", 
              "id": "http://www.grid.ac/institutes/grid.7722.0", 
              "name": [
                "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pich", 
            "givenName": "Oriol", 
            "id": "sg:person.07763174311.65", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07763174311.65"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain", 
              "id": "http://www.grid.ac/institutes/grid.425902.8", 
              "name": [
                "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain", 
                "Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain", 
                "Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lopez-Bigas", 
            "givenName": "Nuria", 
            "id": "sg:person.01232662277.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232662277.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Tumour Profiling Unit, The Institute of Cancer Research, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.18886.3f", 
              "name": [
                "Tumour Profiling Unit, The Institute of Cancer Research, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Matthews", 
            "givenName": "Nik", 
            "id": "sg:person.01006330237.21", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006330237.21"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rao", 
            "givenName": "Sheela", 
            "id": "sg:person.01321127272.55", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01321127272.55"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Watkins", 
            "givenName": "David", 
            "id": "sg:person.0723551231.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723551231.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chau", 
            "givenName": "Ian", 
            "id": "sg:person.01035560774.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035560774.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Starling", 
            "givenName": "Naureen", 
            "id": "sg:person.01136565472.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136565472.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cunningham", 
            "givenName": "David", 
            "id": "sg:person.01320161130.16", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320161130.16"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK", 
              "id": "http://www.grid.ac/institutes/grid.424926.f", 
              "name": [
                "Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK", 
                "Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gerlinger", 
            "givenName": "Marco", 
            "id": "sg:person.0615030103.67", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0615030103.67"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/s41586-019-1689-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1122019643", 
              "https://doi.org/10.1038/s41586-019-1689-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13073-018-0539-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103635246", 
              "https://doi.org/10.1186/s13073-018-0539-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605912", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025463660", 
              "https://doi.org/10.1038/sj.bjc.6605912"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-11037-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117794183", 
              "https://doi.org/10.1038/s41467-019-11037-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-016-0893-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041278818", 
              "https://doi.org/10.1186/s13059-016-0893-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41586-020-1943-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1124597030", 
              "https://doi.org/10.1038/s41586-020-1943-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.2609", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007295122", 
              "https://doi.org/10.1038/nm.2609"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11219", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004846070", 
              "https://doi.org/10.1038/nature11219"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12859-019-3043-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1120775100", 
              "https://doi.org/10.1186/s12859-019-3043-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature12477", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050004918", 
              "https://doi.org/10.1038/nature12477"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13073-017-0434-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085558921", 
              "https://doi.org/10.1186/s13073-017-0434-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-018-04208-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103817397", 
              "https://doi.org/10.1038/s41467-018-04208-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-12594-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1121548145", 
              "https://doi.org/10.1038/s41467-019-12594-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc.2017.69", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091779103", 
              "https://doi.org/10.1038/nrc.2017.69"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms15617", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085929320", 
              "https://doi.org/10.1038/ncomms15617"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3441", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011007538", 
              "https://doi.org/10.1038/ng.3441"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2764", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033967678", 
              "https://doi.org/10.1038/ng.2764"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12859-019-2688-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1113580454", 
              "https://doi.org/10.1186/s12859-019-2688-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11156", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024120060", 
              "https://doi.org/10.1038/nature11156"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41586-019-1907-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1124588398", 
              "https://doi.org/10.1038/s41586-019-1907-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41588-019-0525-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1122669238", 
              "https://doi.org/10.1038/s41588-019-0525-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13059-018-1509-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1106912408", 
              "https://doi.org/10.1186/s13059-018-1509-y"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-05-20", 
        "datePublishedReg": "2021-05-20", 
        "description": "Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41559-021-01470-8", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.7926992", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1284474", 
            "issn": [
              "2397-334X"
            ], 
            "name": "Nature Ecology & Evolution", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "7", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "5"
          }
        ], 
        "keywords": [
          "colorectal cancer", 
          "wild-type colorectal cancer", 
          "shorter progression-free survival", 
          "EGFR driver mutations", 
          "EGFR antibody resistance", 
          "progression-free survival", 
          "KRAS/NRAS", 
          "anti-EGFR antibodies", 
          "mutational signatures", 
          "cetuximab treatment", 
          "progression biopsies", 
          "antibody resistance", 
          "driver mutations", 
          "exome sequencing data", 
          "cancer", 
          "baseline", 
          "specific mutations", 
          "treatment", 
          "mutation load", 
          "cetuximab", 
          "patients", 
          "biopsy", 
          "mutations", 
          "progression", 
          "NRAS", 
          "antibodies", 
          "survival", 
          "predictors", 
          "resistance", 
          "evidence", 
          "mutational mechanisms", 
          "sequencing data", 
          "resistance evolution", 
          "main contributor", 
          "activity", 
          "contributor", 
          "mechanism", 
          "mutagenesis", 
          "data", 
          "new class", 
          "signatures", 
          "adaptive mutagenesis", 
          "results", 
          "questions", 
          "load", 
          "class", 
          "contribution", 
          "evolution"
        ], 
        "name": "Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer", 
        "pagination": "1024-1032", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1138201806"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41559-021-01470-8"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "34017094"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41559-021-01470-8", 
          "https://app.dimensions.ai/details/publication/pub.1138201806"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-10-01T06:49", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_904.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41559-021-01470-8"
      }
    ]
     

    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/s41559-021-01470-8'

    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/s41559-021-01470-8'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41559-021-01470-8'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41559-021-01470-8'


     

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

    309 TRIPLES      21 PREDICATES      100 URIs      70 LITERALS      12 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41559-021-01470-8 schema:about N19ff4a14af1a4e65a1a97b26f2f6c0d4
    2 N4db886ea23114a08bd2d5f5204e2f668
    3 N4fda9d8b040e48afa26e9f87d40415da
    4 N9f075e6cb6974c6281a20dd06cd2556d
    5 Nb8f9310bacee492c8dbbaa980144cc04
    6 anzsrc-for:11
    7 anzsrc-for:1112
    8 schema:author N81a097bb02184ba9806a5eea3940bbbe
    9 schema:citation sg:pub.10.1038/nature11156
    10 sg:pub.10.1038/nature11219
    11 sg:pub.10.1038/nature12477
    12 sg:pub.10.1038/ncomms15617
    13 sg:pub.10.1038/ng.2764
    14 sg:pub.10.1038/ng.3441
    15 sg:pub.10.1038/nm.2609
    16 sg:pub.10.1038/nrc.2017.69
    17 sg:pub.10.1038/s41467-018-04208-6
    18 sg:pub.10.1038/s41467-019-11037-8
    19 sg:pub.10.1038/s41467-019-12594-8
    20 sg:pub.10.1038/s41586-019-1689-y
    21 sg:pub.10.1038/s41586-019-1907-7
    22 sg:pub.10.1038/s41586-020-1943-3
    23 sg:pub.10.1038/s41588-019-0525-5
    24 sg:pub.10.1038/sj.bjc.6605912
    25 sg:pub.10.1186/s12859-019-2688-6
    26 sg:pub.10.1186/s12859-019-3043-7
    27 sg:pub.10.1186/s13059-016-0893-4
    28 sg:pub.10.1186/s13059-018-1509-y
    29 sg:pub.10.1186/s13073-017-0434-0
    30 sg:pub.10.1186/s13073-018-0539-0
    31 schema:datePublished 2021-05-20
    32 schema:datePublishedReg 2021-05-20
    33 schema:description Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor.
    34 schema:genre article
    35 schema:isAccessibleForFree true
    36 schema:isPartOf N9fb135f3ffd747069c062320b385b439
    37 Nc1cd02f066f34ad894b8c6aed1d25d32
    38 sg:journal.1284474
    39 schema:keywords EGFR antibody resistance
    40 EGFR driver mutations
    41 KRAS/NRAS
    42 NRAS
    43 activity
    44 adaptive mutagenesis
    45 anti-EGFR antibodies
    46 antibodies
    47 antibody resistance
    48 baseline
    49 biopsy
    50 cancer
    51 cetuximab
    52 cetuximab treatment
    53 class
    54 colorectal cancer
    55 contribution
    56 contributor
    57 data
    58 driver mutations
    59 evidence
    60 evolution
    61 exome sequencing data
    62 load
    63 main contributor
    64 mechanism
    65 mutagenesis
    66 mutation load
    67 mutational mechanisms
    68 mutational signatures
    69 mutations
    70 new class
    71 patients
    72 predictors
    73 progression
    74 progression biopsies
    75 progression-free survival
    76 questions
    77 resistance
    78 resistance evolution
    79 results
    80 sequencing data
    81 shorter progression-free survival
    82 signatures
    83 specific mutations
    84 survival
    85 treatment
    86 wild-type colorectal cancer
    87 schema:name Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer
    88 schema:pagination 1024-1032
    89 schema:productId N260d1558258e424dbf68d3bfbdf8b900
    90 N37109c2fdb2643dbac9444c19a5dad6f
    91 N9cfe1fffd5d745d2b3a701ff07b165b7
    92 schema:sameAs https://app.dimensions.ai/details/publication/pub.1138201806
    93 https://doi.org/10.1038/s41559-021-01470-8
    94 schema:sdDatePublished 2022-10-01T06:49
    95 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    96 schema:sdPublisher N8e2eef1f7d92415095a3c2d08aa32030
    97 schema:url https://doi.org/10.1038/s41559-021-01470-8
    98 sgo:license sg:explorer/license/
    99 sgo:sdDataset articles
    100 rdf:type schema:ScholarlyArticle
    101 N19ff4a14af1a4e65a1a97b26f2f6c0d4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    102 schema:name Antineoplastic Agents, Immunological
    103 rdf:type schema:DefinedTerm
    104 N260d1558258e424dbf68d3bfbdf8b900 schema:name dimensions_id
    105 schema:value pub.1138201806
    106 rdf:type schema:PropertyValue
    107 N31060fdbd5f64b0a874e949ae754d8bf rdf:first sg:person.0723551231.39
    108 rdf:rest Nda94753e8a244d64b8db03233db101f2
    109 N37109c2fdb2643dbac9444c19a5dad6f schema:name pubmed_id
    110 schema:value 34017094
    111 rdf:type schema:PropertyValue
    112 N4a5ea13fe166406e8a6b7d9af237a8b5 rdf:first sg:person.01006330237.21
    113 rdf:rest Ndad708402f0b49ed82df4f9916680fb7
    114 N4b5db12ad91949c9a5b651baf3d34d38 rdf:first sg:person.01136565472.17
    115 rdf:rest Ncfdd8008e36d4f7dbbaeb4c72b82098e
    116 N4db886ea23114a08bd2d5f5204e2f668 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Cetuximab
    118 rdf:type schema:DefinedTerm
    119 N4fda9d8b040e48afa26e9f87d40415da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Colorectal Neoplasms
    121 rdf:type schema:DefinedTerm
    122 N563a1914db5d4cec9cb0ac2367c8639b rdf:first sg:person.07763174311.65
    123 rdf:rest Ned3e499a7e154cd19d7ece090d808364
    124 N5eac9544a2dc4156ba7c6075003a84a3 rdf:first sg:person.010411247077.27
    125 rdf:rest N563a1914db5d4cec9cb0ac2367c8639b
    126 N81a097bb02184ba9806a5eea3940bbbe rdf:first sg:person.01145246415.46
    127 rdf:rest N90e1de7a44e0475a9000f2f03b3f1fb8
    128 N8e2eef1f7d92415095a3c2d08aa32030 schema:name Springer Nature - SN SciGraph project
    129 rdf:type schema:Organization
    130 N90e1de7a44e0475a9000f2f03b3f1fb8 rdf:first sg:person.01231216510.66
    131 rdf:rest N5eac9544a2dc4156ba7c6075003a84a3
    132 N9cfe1fffd5d745d2b3a701ff07b165b7 schema:name doi
    133 schema:value 10.1038/s41559-021-01470-8
    134 rdf:type schema:PropertyValue
    135 N9f075e6cb6974c6281a20dd06cd2556d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Mutation
    137 rdf:type schema:DefinedTerm
    138 N9fb135f3ffd747069c062320b385b439 schema:volumeNumber 5
    139 rdf:type schema:PublicationVolume
    140 Nb8f9310bacee492c8dbbaa980144cc04 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Humans
    142 rdf:type schema:DefinedTerm
    143 Nc1cd02f066f34ad894b8c6aed1d25d32 schema:issueNumber 7
    144 rdf:type schema:PublicationIssue
    145 Ncfdd8008e36d4f7dbbaeb4c72b82098e rdf:first sg:person.01320161130.16
    146 rdf:rest Nebe4cd2686c84941bcd7d062c0ee7333
    147 Nda94753e8a244d64b8db03233db101f2 rdf:first sg:person.01035560774.45
    148 rdf:rest N4b5db12ad91949c9a5b651baf3d34d38
    149 Ndad708402f0b49ed82df4f9916680fb7 rdf:first sg:person.01321127272.55
    150 rdf:rest N31060fdbd5f64b0a874e949ae754d8bf
    151 Nebe4cd2686c84941bcd7d062c0ee7333 rdf:first sg:person.0615030103.67
    152 rdf:rest rdf:nil
    153 Ned3e499a7e154cd19d7ece090d808364 rdf:first sg:person.01232662277.25
    154 rdf:rest N4a5ea13fe166406e8a6b7d9af237a8b5
    155 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    156 schema:name Medical and Health Sciences
    157 rdf:type schema:DefinedTerm
    158 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    159 schema:name Oncology and Carcinogenesis
    160 rdf:type schema:DefinedTerm
    161 sg:grant.7926992 http://pending.schema.org/fundedItem sg:pub.10.1038/s41559-021-01470-8
    162 rdf:type schema:MonetaryGrant
    163 sg:journal.1284474 schema:issn 2397-334X
    164 schema:name Nature Ecology & Evolution
    165 schema:publisher Springer Nature
    166 rdf:type schema:Periodical
    167 sg:person.01006330237.21 schema:affiliation grid-institutes:grid.18886.3f
    168 schema:familyName Matthews
    169 schema:givenName Nik
    170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006330237.21
    171 rdf:type schema:Person
    172 sg:person.01035560774.45 schema:affiliation grid-institutes:grid.424926.f
    173 schema:familyName Chau
    174 schema:givenName Ian
    175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035560774.45
    176 rdf:type schema:Person
    177 sg:person.010411247077.27 schema:affiliation grid-institutes:grid.18886.3f
    178 schema:familyName Griffiths
    179 schema:givenName Beatrice
    180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010411247077.27
    181 rdf:type schema:Person
    182 sg:person.01136565472.17 schema:affiliation grid-institutes:grid.424926.f
    183 schema:familyName Starling
    184 schema:givenName Naureen
    185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136565472.17
    186 rdf:type schema:Person
    187 sg:person.01145246415.46 schema:affiliation grid-institutes:grid.18886.3f
    188 schema:familyName Woolston
    189 schema:givenName Andrew
    190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01145246415.46
    191 rdf:type schema:Person
    192 sg:person.01231216510.66 schema:affiliation grid-institutes:grid.18886.3f
    193 schema:familyName Barber
    194 schema:givenName Louise J.
    195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01231216510.66
    196 rdf:type schema:Person
    197 sg:person.01232662277.25 schema:affiliation grid-institutes:grid.425902.8
    198 schema:familyName Lopez-Bigas
    199 schema:givenName Nuria
    200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232662277.25
    201 rdf:type schema:Person
    202 sg:person.01320161130.16 schema:affiliation grid-institutes:grid.424926.f
    203 schema:familyName Cunningham
    204 schema:givenName David
    205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320161130.16
    206 rdf:type schema:Person
    207 sg:person.01321127272.55 schema:affiliation grid-institutes:grid.424926.f
    208 schema:familyName Rao
    209 schema:givenName Sheela
    210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01321127272.55
    211 rdf:type schema:Person
    212 sg:person.0615030103.67 schema:affiliation grid-institutes:grid.424926.f
    213 schema:familyName Gerlinger
    214 schema:givenName Marco
    215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0615030103.67
    216 rdf:type schema:Person
    217 sg:person.0723551231.39 schema:affiliation grid-institutes:grid.424926.f
    218 schema:familyName Watkins
    219 schema:givenName David
    220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723551231.39
    221 rdf:type schema:Person
    222 sg:person.07763174311.65 schema:affiliation grid-institutes:grid.7722.0
    223 schema:familyName Pich
    224 schema:givenName Oriol
    225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07763174311.65
    226 rdf:type schema:Person
    227 sg:pub.10.1038/nature11156 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024120060
    228 https://doi.org/10.1038/nature11156
    229 rdf:type schema:CreativeWork
    230 sg:pub.10.1038/nature11219 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004846070
    231 https://doi.org/10.1038/nature11219
    232 rdf:type schema:CreativeWork
    233 sg:pub.10.1038/nature12477 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050004918
    234 https://doi.org/10.1038/nature12477
    235 rdf:type schema:CreativeWork
    236 sg:pub.10.1038/ncomms15617 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085929320
    237 https://doi.org/10.1038/ncomms15617
    238 rdf:type schema:CreativeWork
    239 sg:pub.10.1038/ng.2764 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033967678
    240 https://doi.org/10.1038/ng.2764
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1038/ng.3441 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011007538
    243 https://doi.org/10.1038/ng.3441
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1038/nm.2609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007295122
    246 https://doi.org/10.1038/nm.2609
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1038/nrc.2017.69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091779103
    249 https://doi.org/10.1038/nrc.2017.69
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1038/s41467-018-04208-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103817397
    252 https://doi.org/10.1038/s41467-018-04208-6
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1038/s41467-019-11037-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117794183
    255 https://doi.org/10.1038/s41467-019-11037-8
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1038/s41467-019-12594-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1121548145
    258 https://doi.org/10.1038/s41467-019-12594-8
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1038/s41586-019-1689-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1122019643
    261 https://doi.org/10.1038/s41586-019-1689-y
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/s41586-019-1907-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1124588398
    264 https://doi.org/10.1038/s41586-019-1907-7
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/s41586-020-1943-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1124597030
    267 https://doi.org/10.1038/s41586-020-1943-3
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/s41588-019-0525-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1122669238
    270 https://doi.org/10.1038/s41588-019-0525-5
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/sj.bjc.6605912 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025463660
    273 https://doi.org/10.1038/sj.bjc.6605912
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1186/s12859-019-2688-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113580454
    276 https://doi.org/10.1186/s12859-019-2688-6
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1186/s12859-019-3043-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1120775100
    279 https://doi.org/10.1186/s12859-019-3043-7
    280 rdf:type schema:CreativeWork
    281 sg:pub.10.1186/s13059-016-0893-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041278818
    282 https://doi.org/10.1186/s13059-016-0893-4
    283 rdf:type schema:CreativeWork
    284 sg:pub.10.1186/s13059-018-1509-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1106912408
    285 https://doi.org/10.1186/s13059-018-1509-y
    286 rdf:type schema:CreativeWork
    287 sg:pub.10.1186/s13073-017-0434-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085558921
    288 https://doi.org/10.1186/s13073-017-0434-0
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1186/s13073-018-0539-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103635246
    291 https://doi.org/10.1186/s13073-018-0539-0
    292 rdf:type schema:CreativeWork
    293 grid-institutes:grid.18886.3f schema:alternateName Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK
    294 Tumour Profiling Unit, The Institute of Cancer Research, London, UK
    295 schema:name Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK
    296 Tumour Profiling Unit, The Institute of Cancer Research, London, UK
    297 rdf:type schema:Organization
    298 grid-institutes:grid.424926.f schema:alternateName Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK
    299 schema:name Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, UK
    300 Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, UK
    301 rdf:type schema:Organization
    302 grid-institutes:grid.425902.8 schema:alternateName Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
    303 schema:name Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
    304 Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
    305 Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain
    306 rdf:type schema:Organization
    307 grid-institutes:grid.7722.0 schema:alternateName Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
    308 schema:name Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
    309 rdf:type schema:Organization
     




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


    ...