The role of c-KIT in tumorigenesis:: Evaluation in canine cutaneous mast cell tumors
The role of c-KIT in tumorigenesis:: Evaluation in canine cutaneous mast cell tumors
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DOI：
10.1593/neo.05622
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Kiupel, Matti
中科院分区：
文献类型：
--
作者：
Webster, Joshua D.;Yuzbasiyan-Gurkan, Vilma;Kiupel, Matti
c-KIT原癌基因与几种肿瘤性疾病的发病机制有关，包括人的胃肠道间质瘤和肥大细胞增多症以及犬的肥大细胞瘤（MCT）。皮肤MCT是犬中常见的肿瘤，具有不同的生物学行为。本研究的目的是确定犬MCT中鉴定的c-KIT突变的预后意义以及c-KIT突变、KIT定位和KIT表达水平之间的相关性。对60例MCT进行显微切割和聚合酶链反应，以鉴定c-KIT突变。抗KIT抗体用于KIT定位的免疫组织化学评价。组织微阵列中包括42个MCT，并使用免疫荧光定量KIT表达。具有c-KIT突变的犬MCT与复发性疾病和死亡的发生率增加显著相关。c-KIT突变也与异常蛋白定位显著相关;然而，KIT表达水平与c-KIT突变或蛋白定位变化无关。考虑到犬MCT的高患病率和c-KIT在某些肿瘤的肿瘤发生中的核心作用，犬MCT是表征c-KIT在肿瘤性疾病中作用的极好模型，并且是临床试验中新型治疗药物的潜在靶点。
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.