Familial /sporadic gastrointestinal stromal tumors (GISTs)

2000-06-01   Lidia Larizza  , Alessandro Beghini, PhD 

Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy

Identity

Name

Familial \/sporadic gastrointestinal stromal tumors (GISTs)

Note

a recently described familial cancer syndrome characterized by development of multiple GISTs in different family members

Inheritance

autosomal dominant

Omim

606764

Mesh

D046152

Orphanet

44890 Gastrointestinal stromal tumor

Umls

C0238198

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

    Description

    21 exons

    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

    • To be noted

    Hgmd

    120117

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    94388541998Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.Hirota S et al
    107023942000KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.Lux ML et al
    96976901998Familial gastrointestinal stromal tumours with germline mutation of the KIT gene.Nishida T et al
    106656491999C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.Sakurai S et al
    104854751999Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.Taniguchi M et al

    Citation

    Lidia Larizza ; Alessandro Beghini, PhD

    Familial /sporadic gastrointestinal stromal tumors (GISTs)

    Atlas Genet Cytogenet Oncol Haematol. 2000-06-01

    Online version: http://atlasgeneticsoncology.org/cancer-prone-disease/10029/familial-sporadic-gastrointestinal-stromal-tumors-(gists)

    Historical Card

    1998-09-01 Familial \/sporadic gastrointestinal stromal tumors (GISTs) by  Lidia Larizza,Alessandro Beghini 

    Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy