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狮子(Acinonyx jubatus)和家猫(Felis catus)肥大细胞瘤中的 KIT 突变。

KIT mutations in mast cell tumours from cheetahs (Acinonyx jubatus) and domestic cats (Felis catus).

机构信息

School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, Australia.

Taronga Conservation Society Australia, Taronga Western Plains Zoo, Dubbo, Australia.

出版信息

Vet Comp Oncol. 2021 Jun;19(2):381-392. doi: 10.1111/vco.12683. Epub 2021 Mar 24.

Abstract

Mast cell tumours (MCT) have been documented in numerous species and mutations within the KIT proto-oncogene are implicated in the neoplastic biology of mast cells in humans, dogs and cats. This study determined high KIT gene nucleotide and Kit amino acid sequence homology between several species known to suffer mast cell neoplasia and especially high sequence conservation between the cheetah (Acinonyx jubatus) and domestic cat (Felis catus) KIT sequences. As a result, we hypothesised that KIT mutations would exist in the neoplastic DNA of four cheetahs diagnosed with MCT from a recent case series. PCR and Sanger sequencing identified conservative exon 6 KIT mutations in two of the four cheetahs. The mutations were different between the two cheetahs. Only wild-type DNA in exons 6, 8, 9 and 11 of KIT was observed in the MCTs of the remaining two cheetahs. Twenty cutaneous MCTs from domestic cats were collected for KIT mutation comparison. Twelve tumours possessed a mutation within KIT exons 6, 8 or 9 (60%, 95% CI 38.5%-81.5%). No mutations were detected in exon 11. There was no significant association between domestic feline MCT KIT mutation status and tumour histological grade (traditional schematic, P = .934; Sabattini 2-tier schematic, P = .762) or mitotic index (P = .750). KIT mRNA and Kit protein sequences are conserved across species but the role of KIT in feline MCT pathogenesis is not completely understood.

摘要

肥大细胞瘤(MCT)已在众多物种中被记录,并且 KIT 原癌基因中的突变被认为与人类、犬和猫的肥大细胞瘤的肿瘤生物学有关。本研究确定了几种已知患有肥大细胞瘤的物种之间的高 KIT 基因核苷酸和 Kit 氨基酸序列同源性,特别是在猎豹(Acinonyx jubatus)和家猫(Felis catus)KIT 序列之间存在高度的序列保守性。因此,我们假设在最近的病例系列中诊断为 MCT 的四只猎豹的肿瘤 DNA 中存在 KIT 突变。PCR 和 Sanger 测序在四只猎豹中的两只中鉴定出保守的外显子 6 KIT 突变。这两个猎豹中的突变是不同的。在另外两只猎豹的 MCT 中仅观察到 KIT 外显子 6、8、9 和 11 的野生型 DNA。收集了 20 个来自家猫的皮肤肥大细胞瘤进行 KIT 突变比较。12 个肿瘤在 KIT 外显子 6、8 或 9 中存在突变(60%,95%CI 38.5%-81.5%)。在外显子 11 中未检测到突变。在 domestic feline MCT KIT 突变状态与肿瘤组织学分级(传统示意图,P =.934;Sabattini 2 级示意图,P =.762)或有丝分裂指数(P =.750)之间没有显著关联。KIT mRNA 和 Kit 蛋白序列在物种间是保守的,但 KIT 在猫肥大细胞瘤发病机制中的作用尚未完全阐明。

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