The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors
The c-KIT proto-oncogene has been implicated in the pathogenesis of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and mast cell tumors (MCTs) in canines. Cutaneous MCTs are common neoplasms in dogs and have a variable biologic behavior. The goal o...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558606800199 |
| _version_ | 1818787810769895424 |
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| author | Joshua D. Webster Vilma Yuzbasiyan-Gurkan John B. Kaneene RoseAnn Miller James H. Resau Matti Kiupel |
| author_facet | Joshua D. Webster Vilma Yuzbasiyan-Gurkan John B. Kaneene RoseAnn Miller James H. Resau Matti Kiupel |
| author_sort | Joshua D. Webster |
| collection | DOAJ |
| description | The c-KIT proto-oncogene has been implicated in the pathogenesis of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and mast cell tumors (MCTs) in canines. Cutaneous MCTs are common neoplasms in dogs and have a variable biologic behavior. The goal of this study was to define the prognostic significance of c-KIT mutations identified in canine MCTs and the associations between c-KIT mutations, KIT localization, and KIT expression levels. Microdissection and polymerase chain reaction were performed on 60 MCTs to identify c-KIT mutations. Anti-KIT antibodies were used for immunohistochemical evaluation of KIT localization. Forty-two MCTs were included in a tissue microarray, and KIT expression was quantified using immunofluorescence. Canine MCTs with c-KIT mutations were significantly associated with an increased incidence of recurrent disease and death. c-KIT mutations were also significantly associated with aberrant protein localization; however, the level of KIT expression did not correlate with either c-KIT mutations or changes in protein localization. Considering the high prevalence of canine MCTs and the central role of c-KIT in the tumorigenesis of certain tumors, canine MCTs are an excellent model for characterizing the role of c-KIT in neoplastic diseases and is a potential target for novel therapeutic agents in clinical trials. |
| first_indexed | 2024-12-18T14:13:42Z |
| format | Article |
| id | doaj.art-f57418aa29c544429d31570dd5ca2831 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-18T14:13:42Z |
| publishDate | 2006-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-f57418aa29c544429d31570dd5ca28312022-12-21T21:05:04ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022006-02-018210411110.1593/neo.05622The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell TumorsJoshua D. Webster0Vilma Yuzbasiyan-Gurkan1John B. Kaneene2RoseAnn Miller3James H. Resau4Matti Kiupel5Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAComparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USACenter for Population Medicine, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USACenter for Population Medicine, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAVan Andel Research Institute, Grand Rapids, MI 49503, USAComparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAThe c-KIT proto-oncogene has been implicated in the pathogenesis of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and mast cell tumors (MCTs) in canines. Cutaneous MCTs are common neoplasms in dogs and have a variable biologic behavior. The goal of this study was to define the prognostic significance of c-KIT mutations identified in canine MCTs and the associations between c-KIT mutations, KIT localization, and KIT expression levels. Microdissection and polymerase chain reaction were performed on 60 MCTs to identify c-KIT mutations. Anti-KIT antibodies were used for immunohistochemical evaluation of KIT localization. Forty-two MCTs were included in a tissue microarray, and KIT expression was quantified using immunofluorescence. Canine MCTs with c-KIT mutations were significantly associated with an increased incidence of recurrent disease and death. c-KIT mutations were also significantly associated with aberrant protein localization; however, the level of KIT expression did not correlate with either c-KIT mutations or changes in protein localization. Considering the high prevalence of canine MCTs and the central role of c-KIT in the tumorigenesis of certain tumors, canine MCTs are an excellent model for characterizing the role of c-KIT in neoplastic diseases and is a potential target for novel therapeutic agents in clinical trials.http://www.sciencedirect.com/science/article/pii/S1476558606800199c-KITKITmutationanimal modelcanine |
| spellingShingle | Joshua D. Webster Vilma Yuzbasiyan-Gurkan John B. Kaneene RoseAnn Miller James H. Resau Matti Kiupel The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors Neoplasia: An International Journal for Oncology Research c-KIT KIT mutation animal model canine |
| title | The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors |
| title_full | The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors |
| title_fullStr | The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors |
| title_full_unstemmed | The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors |
| title_short | The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors |
| title_sort | role of c kit in tumorigenesis evaluation in canine cutaneous mast cell tumors |
| topic | c-KIT KIT mutation animal model canine |
| url | http://www.sciencedirect.com/science/article/pii/S1476558606800199 |
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