title: Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases.
abstract: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases.
authors.affiliation: Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lasota
authors.forename: A
authors.initials: A
authors.lastname: Wozniak
authors.forename: M
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: J
authors.initials: J
authors.lastname: Rys
authors.forename: R
authors.initials: R
authors.lastname: Kordek
authors.forename: A
authors.initials: A
authors.lastname: Nassar
authors.forename: L H
authors.initials: LH
authors.lastname: Sobin
authors.forename: M
authors.initials: M
authors.lastname: Miettinen
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence / Q000235:genetics; D005091:Exons; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012016:Reference Values; D017154:Stromal Cells / Q000473:pathology*
chemical_list: D019009:Proto-Oncogene Proteins c-kit