Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats
Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats
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DOI：
10.2460/ajvr.2002.63.1129
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发表时间：
2002-08-01
影响因子：
1
通讯作者：
London, CA
中科院分区：
文献类型：
--
作者：
Dank, G;Chien, MB;London, CA
评价猫脾肥大细胞瘤（MCT）中原癌基因c-kit的激活突变。样本群体-来自加州大学兽医教学医院病理数据库中猫的10份福尔马林固定、石蜡包埋的脾MCT。程序-从肿瘤标本中分离基因组DNA，并对外显子11进行聚合酶链反应（PCR）程序，12,PCR产物经琼脂糖凝胶电泳分析，然后直接测序。结果-我们没有发现突变的质膜结构域（由外显子11和12编码）或催化结构域结论：尽管原癌基因c-kit的突变可能与肿瘤的发生有关，但c-kit基因的突变可能与肿瘤的发生有关。Kit经常出现在犬自然发育的MCT和人类侵袭性肥大细胞增多症中，本文报告的数据证明，通过激活突变导致的Kit功能失调不太可能出现在猫的脾脏MCT中。旨在抑制Kit信号传导的治疗策略（即激酶抑制剂，如伊马替尼[STI 571]）可能对治疗猫的这种疾病没有益处。
Objective-To evaluate splenic mast cell tumors (MCT) of cats for activating mutations in the protooncogene c-kit.Sample Population-10 formalin-fixed, paraffin-embedded splenic MCT from cats in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis.Procedure-Genomic DNA was isolated from tumor specimens, and the polymerase chain reaction (PCR) procedure was performed for exons 11, 12, and 17 The PCR products were analyzed by use of agarose gel electrophoresis and then directly sequenced.Results-We did not identify mutations in the juxtamembrane domain (encoded by exons 11 and 12) or catalytic domain (encoded by exon 17) of c-kit in any of the splenic MCT specimens.Conclusions and Clinical Relevance-Although mutations in the proto-oncogene c-kit occur frequently in naturally developing MCT in dogs and aggressive mastocytosis in humans, the data reported here documented that dysregulation of Kit function through activating mutations is unlikely in splenic MCT of cats. Therapeutic strategies aimed at inhibiting Kit signaling (ie, kinase inhibitors such as imatinib [STI571]) may not be of benefit for the treatment of this disease in cats.