Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase Journal Article


Authors: Sommer, G.; Agosti, V.; Ehlers, I.; Rossi, F.; Corbacioglu, S.; Farkas, J.; Moore, M.; Manova, K.; Antonescu, C. R.; Besmer, P.
Article Title: Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase
Abstract: Oncogenic Kit mutations are found in somatic gastrointestinal (GI) stromal tumors (GISTs) and mastocytosis. A mouse model for the study of constitutive activation of Kit in oncogenesis has been produced by a knock-in strategy introducing a Kit exon 11-activating mutation into the mouse genome based on a mutation found in a case of human familial GIST syndrome. Heterozygous mutant KitV558Δ/+ mice develop symptoms of disease and eventually die from pathology in the GI tract. Patchy hyperplasia of Kit-positive cells is evident within the myenteric plexus of the entire GI tract. Neoplastic lesions indistinguishable from human GISTs were observed in the cecum of the mutant mice with high penetrance. In addition, mast cell numbers in the dorsal skin were increased. Therefore KitV558Δ/+ mice reproduce human familial GISTs, and they may be used as a model for the study of the role and mechanisms of Kit in neoplasia. Importantly, these results demonstrate that constitutive Kit signaling is critical and sufficient for induction of GIST and hyperplasia of interstitial cells of Cajal.
Keywords: immunohistochemistry; controlled study; protein phosphorylation; gene mutation; histopathology; nonhuman; cell proliferation; animal cell; mouse; animals; mice; animal tissue; cell survival; gene targeting; gastrointestinal stromal tumor; stem cell factor; stem cell factor receptor; proto-oncogene proteins c-kit; apoptosis; animal experiment; animal model; protein tyrosine kinase; heterozygote; animalia; mice, transgenic; gastrointestinal neoplasms; oncogene; base sequence; mutagenesis, site-directed; dna primers; point mutation; disease models, animal; site directed mutagenesis; cell hyperplasia; mast cell; cell ultrastructure; myenteric plexus; male; female; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 100
Issue: 11
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2003-05-27
Start Page: 6706
End Page: 6711
Language: English
DOI: 10.1073/pnas.1037763100
PUBMED: 12754375
PROVIDER: scopus
PMCID: PMC164511
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Valter Agosti
    9 Agosti
  2. Cristina R Antonescu
    609 Antonescu
  3. Gunhild Sommer
    6 Sommer
  4. Ferdinando Rossi
    19 Rossi
  5. Malcolm A S Moore
    426 Moore
  6. Peter Besmer
    83 Besmer
  7. Imke Ehlers
    4 Ehlers
  8. Judith   Farkas
    1 Farkas