Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors.
Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors.
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DOI：
10.1186/1471-2407-6-85
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发表时间：
2006-04-01
期刊：
影响因子：
3.8
通讯作者：
Yuzbasiyan-Gurkan V
中科院分区：
文献类型：
--
作者：
Webster JD;Kiupel M;Yuzbasiyan-Gurkan V
c-KIT原癌基因的突变与几种肿瘤性疾病的进展有关，包括人类的胃肠道间质瘤和肥大细胞增多症，以及犬的皮肤肥大细胞瘤（mct）。人类肥大细胞增多症患者的突变主要发生在c-KIT外显子17，该外显子编码其激酶结构域的一部分。相比之下，在大约15%的犬mct中，在c-KIT的近膜结构域中发现了缺失和内部串联重复（ITD）突变。此外，ITD c-KIT突变与犬mct中KIT蛋白的异常定位显著相关。然而，一些犬mct有异常的KIT定位，但缺乏ITD c-KIT突变，这表明其他突变或其他因素可能导致这些肿瘤中异常的KIT定位。为了表征犬mct中c-KIT激酶结构域磷酸转移酶部分突变的普遍性，我们对来自33只狗的33只犬mct的16-20个外显子进行了扩增和测序。此外，为了确定c-KIT外显子17的突变是否导致了缺乏近膜结构域c-KIT突变的mct中的异常KIT定位，从18个显示出异常KIT定位模式但没有ITD c-KIT突变的犬mct中扩增和测序了c-KIT外显子17。在检查的任何mct的外显子16-20中未发现突变或多态性。综上所述，c-KIT激酶结构域磷酸转移酶部分的突变在犬皮肤mct的进展或犬mct中KIT的异常定位中并不起重要作用。
Mutations in the c-KIT proto-oncogene have been implicated in the progression of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs) in canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon 17, which encodes a portion of its kinase domain. In contrast, deletions and internal tandem duplication (ITD) mutations are found in the juxtamembrane domain of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations are significantly associated with aberrant KIT protein localization in canine MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT mutations, suggesting that other mutations or other factors may be responsible for aberrant KIT localization in these tumors. In order to characterize the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase domain in canine MCTs exons 16–20 of 33 canine MCTs from 33 dogs were amplified and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17 are responsible for aberrant KIT localization in MCTs that lack juxtamembrane domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT mutations. No mutations or polymorphisms were identified in exons 16–20 of any of the MCTs examined. In conclusion, mutations in the phospho-transferase portion of c-KIT's kinase domain do not play an important role in the progression of canine cutaneous MCTs, or in the aberrant localization of KIT in canine MCTs.