Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit
Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit
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DOI：
10.1016/s0301-472x(98)00075-7
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发表时间：
1999-04-01
影响因子：
2.6
通讯作者：
Geissler, EN
中科院分区：
文献类型：
--
作者：
London, CA;Galli, SJ;Geissler, EN
自发性肥大细胞瘤(MCT)是犬最常见的恶性肿瘤，占所有犬肿瘤的7%至21%，发病率远远高于人类。这些肿瘤通常表现为侵袭性，转移到局部淋巴结、肝、脾和骨髓。原癌基因c-kit在肥大细胞的发育和功能中起关键作用，已在三个肥大细胞瘤系(P815、RBL和HMC-1)和一些患有不同形式肥大细胞增多症的患者中发现了c-kit激活域的点突变，导致在没有配体结合的情况下导致酪氨酸磷酸化。我们现在证明，尽管来自犬MCT的c-kit不包含先前描述的激活点突变，但在所分析的11个肿瘤中，有5个具有新的突变，包括涉及外显子II和12的串联复制，我们还表明在犬肥大细胞瘤细胞系中检测到的一个这样的重复与c-kit蛋白(KIT)的组成性磷酸化有关，这表明这些突变可能有助于犬MCT的发展或进展。(C)1999年国际实验血液学学会。爱思唯尔科学公司出版。
Spontaneous mast cell tumors (MCT) are the most common malignant neoplasm in the dog, representing between 7% and 21% of all canine tumors, an incidence much higher than that found in humans. These tumors often behave in an aggressive manner, metastasizing to local lymph nodes, liver, spleen, and bone marrow. The proto-oncogene c-kit is known to play a critical role in the development and function of mast cells, Point mutations in the kinase domain of c-kit leading to tyrosine phosphorylation in the absence of ligand binding have been identified in three mastocytoma lines, (P815, RBL, and HMC-1), and some human patients with various forms of mastocytosis. We now demonstrate that although c-kit derived from canine MCT did not contain the previously described activating point mutations, 5 of the 11 tumors analyzed possessed novel mutations consisting of tandem duplications involving exons II and 12, We also show that one such duplication, detected in a canine mastocytoma cell line, was associated with constitutive phosphorylation of c-kit protein (KIT), suggesting that these mutations may contribute to the development or progression of canine MCT. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.