Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11
<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of <it>c-KIT </...
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BMC
2010-10-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/559 |
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| author | Hayes Schantel Kiupel Matti Bartlett Elizabeth Gregory-Bryson Emmalena Yuzbasiyan-Gurkan Vilma |
| author_facet | Hayes Schantel Kiupel Matti Bartlett Elizabeth Gregory-Bryson Emmalena Yuzbasiyan-Gurkan Vilma |
| author_sort | Hayes Schantel |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of <it>c-KIT </it>in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (<it>PDGFRA</it>), all of which have been implicated in human GISTs.</p> <p>Methods</p> <p>Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA</it>, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.</p> <p>Results</p> <p>Of these seventeen cases, six amplicons of exon 11 of <it>c-KIT </it>showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA </it>had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of <it>c-KIT </it>and exons 12 and 14 of <it>PDGFRA</it>.</p> <p>Conclusions</p> <p>The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of <it>c-KIT </it>in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other <it>c-KIT </it>or <it>PDGFRA </it>exons showed any abnormalities in our cases. This finding underlines the critical importance of <it>c-KIT </it>in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in <it>c-KIT </it>implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in <it>c-KIT </it>may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.</p> |
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| spelling | doaj.art-4a3203bb541b47ef8aaa1bce2f2e2ba42022-12-21T20:55:45ZengBMCBMC Cancer1471-24072010-10-0110155910.1186/1471-2407-10-559Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11Hayes SchantelKiupel MattiBartlett ElizabethGregory-Bryson EmmalenaYuzbasiyan-Gurkan Vilma<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of <it>c-KIT </it>in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (<it>PDGFRA</it>), all of which have been implicated in human GISTs.</p> <p>Methods</p> <p>Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA</it>, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.</p> <p>Results</p> <p>Of these seventeen cases, six amplicons of exon 11 of <it>c-KIT </it>showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA </it>had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of <it>c-KIT </it>and exons 12 and 14 of <it>PDGFRA</it>.</p> <p>Conclusions</p> <p>The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of <it>c-KIT </it>in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other <it>c-KIT </it>or <it>PDGFRA </it>exons showed any abnormalities in our cases. This finding underlines the critical importance of <it>c-KIT </it>in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in <it>c-KIT </it>implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in <it>c-KIT </it>may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.</p>http://www.biomedcentral.com/1471-2407/10/559 |
| spellingShingle | Hayes Schantel Kiupel Matti Bartlett Elizabeth Gregory-Bryson Emmalena Yuzbasiyan-Gurkan Vilma Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 BMC Cancer |
| title | Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 |
| title_full | Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 |
| title_fullStr | Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 |
| title_full_unstemmed | Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 |
| title_short | Canine and human gastrointestinal stromal tumors display similar mutations in <it>c-KIT</it> exon 11 |
| title_sort | canine and human gastrointestinal stromal tumors display similar mutations in it c kit it exon 11 |
| url | http://www.biomedcentral.com/1471-2407/10/559 |
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