title: Tyrosine kinase mutations in gastrointestinal stromal tumors in a nation-wide study in Iceland.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. It is characterized by activating mutations in the tyrosine kinase genes c-kit or PDGFRA. This study examined the mutation rate and type in a population-based material. All gastrointestinal mesenchymal tumors over the years 1990-2004 were evaluated and GIST tumors identified using immunohistochemistry (c-kit) and conventional pathologic parameters. Paraffin sections from all tumors were subjected to mutation analysis on exons 9, 11, 13 and 17 of the c-kit gene and exons 12 and 18 of the PDGFRA gene. To screen for mutations, we used a highly sensitive conformation-sensitive gel electrophoresis (CSGE) and to define the mutated alleles, we employed direct automated DNA sequencing. All c-kit-positive gastrointestinal mesenchymal tumors were entered into the study. Fifty-six tumors from 55 patients were analyzed. Mutations were found in 52 tumors representing a 92.9% mutational rate. Most of the mutations were found in c-kit exon 11 (76.8%), followed by c-kit exon 9 (10.7%). PDGFRA mutations were only found in three tumors. No correlation of mutation type with biologic behavior was found. This population-based study, using a sensitive CSGE method, identifies mutations in the great majority of patients with GIST.
authors: Department of Genetics and Molecular Medicine, University of Iceland, Iceland.
authors: Geir
authors: G
authors: Tryggvason
authors: Bylgja
authors: B
authors: Hilmarsdottir
authors: Guethmundur H
authors: GH
authors: Gunnarsson
authors: Jón Jóhannes
authors: JJ
authors: Jónsson
authors: Jón G
authors: JG
authors: Jónasson
authors: Magnús K
authors: MK
authors: Magnússon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007055:Iceland; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha