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Tyrosine kinase mutations in gastrointestinal stromal tumors in a nation-wide study in Iceland.

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Authors
Tryggvason, G
Hilmarsdottir, B
Gunnarsson, G H
Jonsson, J J
Jonasson, J G
Magnusson, M K
Issue Date
2010-09-01

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AMPIS. 2010, 118(9):648-56
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.
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http://dx.doi.org/10.1111/j.1600-0463.2010.02643.x
ae974a485f413a2113503eed53cd6c53
10.1111/j.1600-0463.2010.02643.x
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