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Familial /sporadic gastrointestinal stromal tumors (GISTs)

Written1998-09Lidia Larizza, Alessandro Beghini
Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy
Updated2000-06Lidia Larizza, Alessandro Beghini
Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy

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Identity

Atlas_Id 10029
Genes implicated inKIT  PDGFRA  SDHB  SDHC  
Note a recently described familial cancer syndrome characterized by development of multiple GISTs in different family members
Inheritance autosomal dominant

Clinics

Phenotype and clinics
  • symptoms are attributable to development of benign and malignant GISTs
  • hyperpigmentation and mast-cell disease may be associated
  • etiology : GISTs originate from the CD34+/KIT+ interstitial cells of Cajal (ICCs) which development depends on the SCF/KIT interaction; germline/somatic KIT mutations in familial/solitary GISTs
  • pathology : mesenchymal tumours developped in the gastrointestinal wall mainly characterized by positivity for both KIT and CD34; precursor tumour cells are likely ICCs that are located in and near the circular muscle layer of the stomach, small intestine and large intestine
  • Genes involved and Proteins

    Gene NameKIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)
    Location 4q12
    DNA/RNA
    Description 21 exons
    Protein
    Description transmembrane SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains
    Mutations
    Note see diagram Gain-of-function mutations
    Germinal small deletion of one of two consecutive valine residues (codon 559 or 560, GTTGTT)
    Somatic
  • simple in frame deletions, point mutations, deletion and point mutations are mainly clustered in exon 11 (from codon 550 to 584), but a few have been also identified in exon 9 and exon 13; all mutations are predicted to lead to constitutive phosphorylation and kinase activation
  • the percentage of GISTs positive for c-kit mutations in exon 11 has been estimated to be 57%
  • use of c-kit mutation as unfavourable prognostic marker is under debate

  • Bibliography

    Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
    Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y
    Science (New York, N.Y.). 1998 ; 279 (5350) : 577-580.
    PMID 9438854
     
    KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.
    Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA
    The American journal of pathology. 2000 ; 156 (3) : 791-795.
    PMID 10702394
     
    Familial gastrointestinal stromal tumours with germline mutation of the KIT gene.
    Nishida T, Hirota S, Taniguchi M, Hashimoto K, Isozaki K, Nakamura H, Kanakura Y, Tanaka T, Takabayashi A, Matsuda H, Kitamura Y
    Nature genetics. 1998 ; 19 (4) : 323-324.
    PMID 9697690
     
    C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.
    Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M
    Japanese journal of cancer research : Gann. 1999 ; 90 (12) : 1321-1328.
    PMID 10665649
     
    Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.
    Taniguchi M, Nishida T, Hirota S, Isozaki K, Ito T, Nomura T, Matsuda H, Kitamura Y
    Cancer research. 1999 ; 59 (17) : 4297-4300.
    PMID 10485475
     

    Citation

    This paper should be referenced as such :
    Larizza, L ; Beghini, A
    Familial /sporadic gastrointestinal stromal tumors (GISTs)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):155-156.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/GastroISTID10029.html
    History of this paper:
    Larizza, L ; Beghini, A. Familial gastrointestinal stromal tumors (GISTs). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):43-43.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37492/09-1998-GastroISTID10029.pdf


    External links

    OMIM606764
    OrphanetGastrointestinal stromal tumor
    MeSHD046152  
    MedGenD046152  
    UMLSC0238198  
    ICD-10C26.9  
    HGMD120117
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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