title: Mutations in exon 11 of the c-kit gene in a myogenic tumor and a neurogenic tumor as well as in gastrointestinal stromal tumors. Utility of c-kit mutation as a prognostic biomarker for gastrointestinal mesenchymal tumor.
abstract: OBJECTIVE
  Gain-of-function mutations in exons 9, 11 and 13 of the c-kit gene in gastrointestinal stromal tumors (GISTs) have been identified, and it has been reported that the prognosis is worse for patients with mutation-positive GISTs than for those with mutation-negative GISTs. We studied c-kit mutations in gastrointestinal mesenchymal tumors. By chance, the c-kit mutation in exon 11 was found in myogenic and neurogenic tumors as well as in GISTs. Furthermore, we studied the clinical prognostic utility of these mutations.
  
  
  METHODS
  Ten gastrointestinal mesenchymal tumors were stained with HE and immunohistochemically analyzed with alpha-smooth muscle actin, S-100 protein, CD34 and c-kit. In these tumors, as well as in 11 cases of leiomyomas, PCR-amplified DNA from the juxtamembrane (JM) domain of exon 11, the extracellular domain of exon 9 and the tyrosine kinase domain 1 of exon 13 showed a high frequency of c-kit mutation and was sequenced.
  
  
  RESULTS
  Although c-kit mutations have previously been reported only in GISTs, we found c-kit mutations in the JM domain of exon 11 in one myogenic and one neurogenic tumor as well as in two GISTs. No c-kit mutation was seen in the 11 cases of leiomyomas. In addition, all four cases with c-kit mutation in exon 11 suffered a relapse sooner than the other cases without c-kit mutations.
  
  
  CONCLUSIONS
  Clinically, the prognosis was worse for the patients with mutation-positive gastrointestinal mesenchymal tumors than for those with mutation-negative tumors. We therefore conclude that the gain-of-function mutation in exon 11 of the c-kit gene is an important prognostic factor for gastrointestinal mesenchymal tumors, including myogenic and neurogenic tumors as well as GISTs.
authors.affiliation: Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. yosann10k@hotmail.com
authors.forename: Rie
authors.initials: R
authors.lastname: Yasuoka
authors.forename: Chohei
authors.initials: C
authors.lastname: Sakakura
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shimomura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fujita
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Hideki
authors.initials: H
authors.lastname: Aragane
authors.forename: Akeo
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Masamichi
authors.initials: M
authors.lastname: Bamba
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Abe
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D007889:Leiomyoma / Q000235:genetics; D008297:Male; D008648:Mesoderm; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009379:Neoplasms, Muscle Tissue / Q000235:genetics*; D009380:Neoplasms, Nerve Tissue / Q000235:genetics*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017154:Stromal Cells
chemical_list: D019009:Proto-Oncogene Proteins c-kit