Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-09-13

AUTHORS

Jirina Bartkova, Per Guldberg, Kirsten Grønbæk, Karen Koed, Hanne Primdahl, Klaus Møller, Jiri Lukas, Torben F Ørntoft, Jiri Bartek

ABSTRACT

Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage. Defects of Chk2 occur in subsets of diverse sporadic malignancies and predispose to several types of hereditary carcinomas. However, the status of Chk2 in tumours of the urinary bladder remains unknown. Here, we report that among 58 advanced (grade T2–T4) human bladder carcinomas, immunohistochemical analysis revealed tumour-specific reduction or lack of Chk2 protein in 6 (10.3%) cases. Genetic analysis of the latter subset showed that a Chk2-negative carcinoma #668 harboured a truncating mutation 1100delC, in one Chk2 allele and loss of the corresponding second allele. The 1100delC mutation was also found in the germ line of this patient. Sequencing of TP53 in tumour #668 identified two missense mutations. Furthermore, the vast majority of the tumours showed ‘unscheduled’ activatory phosphorylation on Thr68 of Chk2 in the absence of any DNA-damaging treatment. Our results indicate that the otherwise dormant DNA damage signal transducer Chk2 is aberrantly and constitutively activated in invasive urinary bladder carcinomas, and that such likely proapoptotic checkpoint signalling can be disabled by inactivation of Chk2 and/or p53 tumour suppressors in subsets of these tumours. More... »

PAGES

8545-8551

References to SciGraph publications

  • 2000-09-19. Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1 in NATURE CELL BIOLOGY
  • 2002-11-26. CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours in BRITISH JOURNAL OF CANCER
  • 2002-11-25. 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer in NATURE CELL BIOLOGY
  • 2003-11-11. CHEK2 variants associate with hereditary prostate cancer in BRITISH JOURNAL OF CANCER
  • 2002-02-26. Analysis of CHK2 in vulval neoplasia in BRITISH JOURNAL OF CANCER
  • 2001-09. Chk2 tumour suppressor protein in human spermatogenesis and testicular germ-cell tumours in ONCOGENE
  • 2001-05-01. Genome maintenance mechanisms for preventing cancer in NATURE
  • 2001-12. Chk2 kinase — a busy messenger in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2003-11-05. A DNA damage checkpoint response in telomere-initiated senescence in NATURE
  • 2001-03. DNA double-strand breaks: signaling, repair and the cancer connection in NATURE GENETICS
  • 2002-04-22. Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations in NATURE GENETICS
  • 2000-12. The many substrates and functions of ATM in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2002-02-21. Concomitant inactivation of p53 and Chk2 in breast cancer in ONCOGENE
  • 2001-09-12. Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway in ONCOGENE
  • 2003-03. ATM and related protein kinases: safeguarding genome integrity in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1207878

    DOI

    http://dx.doi.org/10.1038/sj.onc.1207878

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1036176291

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15361851


    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": "Carcinoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Checkpoint Kinase 2", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Primers", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunohistochemistry", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein-Serine-Threonine Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Urinary Bladder Neoplasms", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bartkova", 
            "givenName": "Jirina", 
            "id": "sg:person.0742723433.90", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742723433.90"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Guldberg", 
            "givenName": "Per", 
            "id": "sg:person.0760021664.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760021664.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gr\u00f8nb\u00e6k", 
            "givenName": "Kirsten", 
            "id": "sg:person.01112774027.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112774027.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.154185.c", 
              "name": [
                "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Koed", 
            "givenName": "Karen", 
            "id": "sg:person.0625415601.82", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625415601.82"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.154185.c", 
              "name": [
                "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Primdahl", 
            "givenName": "Hanne", 
            "id": "sg:person.01361543025.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01361543025.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.154185.c", 
              "name": [
                "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "M\u00f8ller", 
            "givenName": "Klaus", 
            "id": "sg:person.01245215436.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245215436.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lukas", 
            "givenName": "Jiri", 
            "id": "sg:person.01235271253.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235271253.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.154185.c", 
              "name": [
                "Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "\u00d8rntoft", 
            "givenName": "Torben F", 
            "id": "sg:person.01066435117.21", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066435117.21"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bartek", 
            "givenName": "Jiri", 
            "id": "sg:person.01167156053.40", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167156053.40"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nrc1011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026716666", 
              "https://doi.org/10.1038/nrc1011"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6601425", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052868427", 
              "https://doi.org/10.1038/sj.bjc.6601425"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35043058", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037972283", 
              "https://doi.org/10.1038/35043058"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng879", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012667501", 
              "https://doi.org/10.1038/ng879"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35036406", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006836350", 
              "https://doi.org/10.1038/35036406"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35103059", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005636144", 
              "https://doi.org/10.1038/35103059"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1204811", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039619177", 
              "https://doi.org/10.1038/sj.onc.1204811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6600637", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026378522", 
              "https://doi.org/10.1038/sj.bjc.6600637"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35077232", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027480321", 
              "https://doi.org/10.1038/35077232"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6600131", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015116490", 
              "https://doi.org/10.1038/sj.bjc.6600131"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1204746", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038244597", 
              "https://doi.org/10.1038/sj.onc.1204746"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/85798", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036425682", 
              "https://doi.org/10.1038/85798"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature02118", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014616827", 
              "https://doi.org/10.1038/nature02118"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1205207", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030940898", 
              "https://doi.org/10.1038/sj.onc.1205207"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb892", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029003147", 
              "https://doi.org/10.1038/ncb892"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2004-09-13", 
        "datePublishedReg": "2004-09-13", 
        "description": "Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage. Defects of Chk2 occur in subsets of diverse sporadic malignancies and predispose to several types of hereditary carcinomas. However, the status of Chk2 in tumours of the urinary bladder remains unknown. Here, we report that among 58 advanced (grade T2\u2013T4) human bladder carcinomas, immunohistochemical analysis revealed tumour-specific reduction or lack of Chk2 protein in 6 (10.3%) cases. Genetic analysis of the latter subset showed that a Chk2-negative carcinoma #668 harboured a truncating mutation 1100delC, in one Chk2 allele and loss of the corresponding second allele. The 1100delC mutation was also found in the germ line of this patient. Sequencing of TP53 in tumour #668 identified two missense mutations. Furthermore, the vast majority of the tumours showed \u2018unscheduled\u2019 activatory phosphorylation on Thr68 of Chk2 in the absence of any DNA-damaging treatment. Our results indicate that the otherwise dormant DNA damage signal transducer Chk2 is aberrantly and constitutively activated in invasive urinary bladder carcinomas, and that such likely proapoptotic checkpoint signalling can be disabled by inactivation of Chk2 and/or p53 tumour suppressors in subsets of these tumours.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/sj.onc.1207878", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "52", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "23"
          }
        ], 
        "keywords": [
          "tumor suppressor", 
          "genome integrity checkpoint", 
          "inactivation of Chk2", 
          "cell-cycle progression", 
          "DNA-damaging treatment", 
          "checkpoint kinase 2", 
          "tumor-specific reduction", 
          "p53 tumor suppressor", 
          "checkpoint signaling", 
          "Sequencing of TP53", 
          "germ line", 
          "Chk2 protein", 
          "DNA repair", 
          "activatory phosphorylation", 
          "signal transducer", 
          "Chk2", 
          "genetic analysis", 
          "kinase 2", 
          "DNA damage", 
          "cell death", 
          "bladder carcinoma", 
          "second allele", 
          "invasive urinary bladder carcinomas", 
          "advanced urinary bladder cancer", 
          "sporadic malignancies", 
          "missense mutations", 
          "suppressor", 
          "urinary bladder cancer", 
          "urinary bladder carcinoma", 
          "human bladder carcinoma", 
          "mutations", 
          "alleles", 
          "bladder cancer", 
          "hereditary carcinoma", 
          "urinary bladder", 
          "immunohistochemical analysis", 
          "carcinoma", 
          "latter subset", 
          "Thr68", 
          "tumors", 
          "phosphorylation", 
          "checkpoint", 
          "sequencing", 
          "signaling", 
          "protein", 
          "inactivation", 
          "vast majority", 
          "TP53", 
          "subset", 
          "patients", 
          "malignancy", 
          "bladder", 
          "cancer", 
          "progression", 
          "repair", 
          "aberrations", 
          "death", 
          "treatment", 
          "lines", 
          "absence", 
          "defects", 
          "transducer", 
          "status", 
          "analysis", 
          "majority", 
          "damage", 
          "response", 
          "loss", 
          "cases", 
          "lack", 
          "reduction", 
          "types", 
          "results", 
          "integrity checkpoints", 
          "Defects of Chk2", 
          "diverse sporadic malignancies", 
          "status of Chk2", 
          "advanced (grade T2\u2013T4) human bladder carcinomas", 
          "Chk2-negative carcinoma", 
          "truncating mutation 1100delC", 
          "mutation 1100delC", 
          "Chk2 allele", 
          "Thr68 of Chk2", 
          "dormant DNA damage signal transducer Chk2", 
          "DNA damage signal transducer Chk2", 
          "damage signal transducer Chk2", 
          "signal transducer Chk2", 
          "transducer Chk2", 
          "such likely proapoptotic checkpoint signalling", 
          "likely proapoptotic checkpoint signalling", 
          "proapoptotic checkpoint signalling", 
          "Chk2 tumour suppressor"
        ], 
        "name": "Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer", 
        "pagination": "8545-8551", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1036176291"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/sj.onc.1207878"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "15361851"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/sj.onc.1207878", 
          "https://app.dimensions.ai/details/publication/pub.1036176291"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2021-12-01T19:16", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20211201/entities/gbq_results/article/article_393.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/sj.onc.1207878"
      }
    ]
     

    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/sj.onc.1207878'

    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/sj.onc.1207878'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1207878'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1207878'


     

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

    301 TRIPLES      22 PREDICATES      140 URIs      117 LITERALS      14 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/sj.onc.1207878 schema:about N125bd2b6dfb6424aa3cf51ece4ca68c2
    2 N27baab590e2841298ab74fef3472a483
    3 N7e2220cec6fe498f802730fdc7994f18
    4 N82e65938050e46f591694f49a01f482e
    5 N843de356f4614f4a8e10815a461beb9a
    6 N8ceb27951a4d4711b2851c7004a1b8d6
    7 Nd24c0c40f19e490b9659561214003d5c
    8 anzsrc-for:11
    9 anzsrc-for:1112
    10 schema:author N991b8a75d9d741a6aeec13f34cc9a25e
    11 schema:citation sg:pub.10.1038/35036406
    12 sg:pub.10.1038/35043058
    13 sg:pub.10.1038/35077232
    14 sg:pub.10.1038/35103059
    15 sg:pub.10.1038/85798
    16 sg:pub.10.1038/nature02118
    17 sg:pub.10.1038/ncb892
    18 sg:pub.10.1038/ng879
    19 sg:pub.10.1038/nrc1011
    20 sg:pub.10.1038/sj.bjc.6600131
    21 sg:pub.10.1038/sj.bjc.6600637
    22 sg:pub.10.1038/sj.bjc.6601425
    23 sg:pub.10.1038/sj.onc.1204746
    24 sg:pub.10.1038/sj.onc.1204811
    25 sg:pub.10.1038/sj.onc.1205207
    26 schema:datePublished 2004-09-13
    27 schema:datePublishedReg 2004-09-13
    28 schema:description Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage. Defects of Chk2 occur in subsets of diverse sporadic malignancies and predispose to several types of hereditary carcinomas. However, the status of Chk2 in tumours of the urinary bladder remains unknown. Here, we report that among 58 advanced (grade T2–T4) human bladder carcinomas, immunohistochemical analysis revealed tumour-specific reduction or lack of Chk2 protein in 6 (10.3%) cases. Genetic analysis of the latter subset showed that a Chk2-negative carcinoma #668 harboured a truncating mutation 1100delC, in one Chk2 allele and loss of the corresponding second allele. The 1100delC mutation was also found in the germ line of this patient. Sequencing of TP53 in tumour #668 identified two missense mutations. Furthermore, the vast majority of the tumours showed ‘unscheduled’ activatory phosphorylation on Thr68 of Chk2 in the absence of any DNA-damaging treatment. Our results indicate that the otherwise dormant DNA damage signal transducer Chk2 is aberrantly and constitutively activated in invasive urinary bladder carcinomas, and that such likely proapoptotic checkpoint signalling can be disabled by inactivation of Chk2 and/or p53 tumour suppressors in subsets of these tumours.
    29 schema:genre article
    30 schema:inLanguage en
    31 schema:isAccessibleForFree true
    32 schema:isPartOf N56b82f0ee2414567975c332fab3c1c52
    33 N6843bfcc30254ebe821abf125e87ed79
    34 sg:journal.1097543
    35 schema:keywords Chk2
    36 Chk2 allele
    37 Chk2 protein
    38 Chk2 tumour suppressor
    39 Chk2-negative carcinoma
    40 DNA damage
    41 DNA damage signal transducer Chk2
    42 DNA repair
    43 DNA-damaging treatment
    44 Defects of Chk2
    45 Sequencing of TP53
    46 TP53
    47 Thr68
    48 Thr68 of Chk2
    49 aberrations
    50 absence
    51 activatory phosphorylation
    52 advanced (grade T2–T4) human bladder carcinomas
    53 advanced urinary bladder cancer
    54 alleles
    55 analysis
    56 bladder
    57 bladder cancer
    58 bladder carcinoma
    59 cancer
    60 carcinoma
    61 cases
    62 cell death
    63 cell-cycle progression
    64 checkpoint
    65 checkpoint kinase 2
    66 checkpoint signaling
    67 damage
    68 damage signal transducer Chk2
    69 death
    70 defects
    71 diverse sporadic malignancies
    72 dormant DNA damage signal transducer Chk2
    73 genetic analysis
    74 genome integrity checkpoint
    75 germ line
    76 hereditary carcinoma
    77 human bladder carcinoma
    78 immunohistochemical analysis
    79 inactivation
    80 inactivation of Chk2
    81 integrity checkpoints
    82 invasive urinary bladder carcinomas
    83 kinase 2
    84 lack
    85 latter subset
    86 likely proapoptotic checkpoint signalling
    87 lines
    88 loss
    89 majority
    90 malignancy
    91 missense mutations
    92 mutation 1100delC
    93 mutations
    94 p53 tumor suppressor
    95 patients
    96 phosphorylation
    97 proapoptotic checkpoint signalling
    98 progression
    99 protein
    100 reduction
    101 repair
    102 response
    103 results
    104 second allele
    105 sequencing
    106 signal transducer
    107 signal transducer Chk2
    108 signaling
    109 sporadic malignancies
    110 status
    111 status of Chk2
    112 subset
    113 such likely proapoptotic checkpoint signalling
    114 suppressor
    115 transducer
    116 transducer Chk2
    117 treatment
    118 truncating mutation 1100delC
    119 tumor suppressor
    120 tumor-specific reduction
    121 tumors
    122 types
    123 urinary bladder
    124 urinary bladder cancer
    125 urinary bladder carcinoma
    126 vast majority
    127 schema:name Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer
    128 schema:pagination 8545-8551
    129 schema:productId N5ddbef4368c545a4bb8551bae7342613
    130 N6e92f362e4ed4b9b84220d9a92765b2e
    131 Nc5f8c9b182f1471780e03b3eb8d4efac
    132 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036176291
    133 https://doi.org/10.1038/sj.onc.1207878
    134 schema:sdDatePublished 2021-12-01T19:16
    135 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    136 schema:sdPublisher N735e074c3fb844b590d4b33a13489164
    137 schema:url https://doi.org/10.1038/sj.onc.1207878
    138 sgo:license sg:explorer/license/
    139 sgo:sdDataset articles
    140 rdf:type schema:ScholarlyArticle
    141 N125bd2b6dfb6424aa3cf51ece4ca68c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Urinary Bladder Neoplasms
    143 rdf:type schema:DefinedTerm
    144 N13e2ad6c6ec54fc789de965280548006 rdf:first sg:person.01235271253.45
    145 rdf:rest N8db9540afd904fd58a433e50a2968dbc
    146 N27baab590e2841298ab74fef3472a483 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    147 schema:name Immunohistochemistry
    148 rdf:type schema:DefinedTerm
    149 N4942703839834f0b91fee83ccd9cca5f rdf:first sg:person.0625415601.82
    150 rdf:rest N9168c5ad68ed45fc98d1d693a86cdc38
    151 N56b82f0ee2414567975c332fab3c1c52 schema:issueNumber 52
    152 rdf:type schema:PublicationIssue
    153 N5ddbef4368c545a4bb8551bae7342613 schema:name dimensions_id
    154 schema:value pub.1036176291
    155 rdf:type schema:PropertyValue
    156 N6843bfcc30254ebe821abf125e87ed79 schema:volumeNumber 23
    157 rdf:type schema:PublicationVolume
    158 N6e92f362e4ed4b9b84220d9a92765b2e schema:name doi
    159 schema:value 10.1038/sj.onc.1207878
    160 rdf:type schema:PropertyValue
    161 N735e074c3fb844b590d4b33a13489164 schema:name Springer Nature - SN SciGraph project
    162 rdf:type schema:Organization
    163 N7e2220cec6fe498f802730fdc7994f18 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Humans
    165 rdf:type schema:DefinedTerm
    166 N82e65938050e46f591694f49a01f482e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name DNA Primers
    168 rdf:type schema:DefinedTerm
    169 N843de356f4614f4a8e10815a461beb9a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Checkpoint Kinase 2
    171 rdf:type schema:DefinedTerm
    172 N8ceb27951a4d4711b2851c7004a1b8d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Carcinoma
    174 rdf:type schema:DefinedTerm
    175 N8db9540afd904fd58a433e50a2968dbc rdf:first sg:person.01066435117.21
    176 rdf:rest Ne5736192f89b49babda65997b131db46
    177 N9168c5ad68ed45fc98d1d693a86cdc38 rdf:first sg:person.01361543025.45
    178 rdf:rest Ne953570ccc8948a3b24d0bed938df449
    179 N91c7915e1d9f40cb95325a3c776db73d rdf:first sg:person.01112774027.77
    180 rdf:rest N4942703839834f0b91fee83ccd9cca5f
    181 N991b8a75d9d741a6aeec13f34cc9a25e rdf:first sg:person.0742723433.90
    182 rdf:rest Ne25ff1a2cf7e4eccb32342c5a9bd9e01
    183 Nc5f8c9b182f1471780e03b3eb8d4efac schema:name pubmed_id
    184 schema:value 15361851
    185 rdf:type schema:PropertyValue
    186 Nd24c0c40f19e490b9659561214003d5c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Protein-Serine-Threonine Kinases
    188 rdf:type schema:DefinedTerm
    189 Ne25ff1a2cf7e4eccb32342c5a9bd9e01 rdf:first sg:person.0760021664.46
    190 rdf:rest N91c7915e1d9f40cb95325a3c776db73d
    191 Ne5736192f89b49babda65997b131db46 rdf:first sg:person.01167156053.40
    192 rdf:rest rdf:nil
    193 Ne953570ccc8948a3b24d0bed938df449 rdf:first sg:person.01245215436.34
    194 rdf:rest N13e2ad6c6ec54fc789de965280548006
    195 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    196 schema:name Medical and Health Sciences
    197 rdf:type schema:DefinedTerm
    198 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    199 schema:name Oncology and Carcinogenesis
    200 rdf:type schema:DefinedTerm
    201 sg:journal.1097543 schema:issn 0950-9232
    202 1476-5594
    203 schema:name Oncogene
    204 schema:publisher Springer Nature
    205 rdf:type schema:Periodical
    206 sg:person.01066435117.21 schema:affiliation grid-institutes:grid.154185.c
    207 schema:familyName Ørntoft
    208 schema:givenName Torben F
    209 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066435117.21
    210 rdf:type schema:Person
    211 sg:person.01112774027.77 schema:affiliation grid-institutes:grid.5254.6
    212 schema:familyName Grønbæk
    213 schema:givenName Kirsten
    214 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112774027.77
    215 rdf:type schema:Person
    216 sg:person.01167156053.40 schema:affiliation grid-institutes:grid.5254.6
    217 schema:familyName Bartek
    218 schema:givenName Jiri
    219 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01167156053.40
    220 rdf:type schema:Person
    221 sg:person.01235271253.45 schema:affiliation grid-institutes:grid.5254.6
    222 schema:familyName Lukas
    223 schema:givenName Jiri
    224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235271253.45
    225 rdf:type schema:Person
    226 sg:person.01245215436.34 schema:affiliation grid-institutes:grid.154185.c
    227 schema:familyName Møller
    228 schema:givenName Klaus
    229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245215436.34
    230 rdf:type schema:Person
    231 sg:person.01361543025.45 schema:affiliation grid-institutes:grid.154185.c
    232 schema:familyName Primdahl
    233 schema:givenName Hanne
    234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01361543025.45
    235 rdf:type schema:Person
    236 sg:person.0625415601.82 schema:affiliation grid-institutes:grid.154185.c
    237 schema:familyName Koed
    238 schema:givenName Karen
    239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625415601.82
    240 rdf:type schema:Person
    241 sg:person.0742723433.90 schema:affiliation grid-institutes:grid.5254.6
    242 schema:familyName Bartkova
    243 schema:givenName Jirina
    244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742723433.90
    245 rdf:type schema:Person
    246 sg:person.0760021664.46 schema:affiliation grid-institutes:grid.5254.6
    247 schema:familyName Guldberg
    248 schema:givenName Per
    249 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0760021664.46
    250 rdf:type schema:Person
    251 sg:pub.10.1038/35036406 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006836350
    252 https://doi.org/10.1038/35036406
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1038/35043058 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037972283
    255 https://doi.org/10.1038/35043058
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1038/35077232 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027480321
    258 https://doi.org/10.1038/35077232
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1038/35103059 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005636144
    261 https://doi.org/10.1038/35103059
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/85798 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036425682
    264 https://doi.org/10.1038/85798
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.1038/nature02118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014616827
    267 https://doi.org/10.1038/nature02118
    268 rdf:type schema:CreativeWork
    269 sg:pub.10.1038/ncb892 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029003147
    270 https://doi.org/10.1038/ncb892
    271 rdf:type schema:CreativeWork
    272 sg:pub.10.1038/ng879 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012667501
    273 https://doi.org/10.1038/ng879
    274 rdf:type schema:CreativeWork
    275 sg:pub.10.1038/nrc1011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026716666
    276 https://doi.org/10.1038/nrc1011
    277 rdf:type schema:CreativeWork
    278 sg:pub.10.1038/sj.bjc.6600131 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015116490
    279 https://doi.org/10.1038/sj.bjc.6600131
    280 rdf:type schema:CreativeWork
    281 sg:pub.10.1038/sj.bjc.6600637 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026378522
    282 https://doi.org/10.1038/sj.bjc.6600637
    283 rdf:type schema:CreativeWork
    284 sg:pub.10.1038/sj.bjc.6601425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052868427
    285 https://doi.org/10.1038/sj.bjc.6601425
    286 rdf:type schema:CreativeWork
    287 sg:pub.10.1038/sj.onc.1204746 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038244597
    288 https://doi.org/10.1038/sj.onc.1204746
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1038/sj.onc.1204811 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039619177
    291 https://doi.org/10.1038/sj.onc.1204811
    292 rdf:type schema:CreativeWork
    293 sg:pub.10.1038/sj.onc.1205207 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030940898
    294 https://doi.org/10.1038/sj.onc.1205207
    295 rdf:type schema:CreativeWork
    296 grid-institutes:grid.154185.c schema:alternateName Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark
    297 schema:name Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus, Denmark
    298 rdf:type schema:Organization
    299 grid-institutes:grid.5254.6 schema:alternateName Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
    300 schema:name Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
    301 rdf:type schema:Organization
     




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


    ...