Abstract Recent studies have demonstrated a significant role of mitochondrial DNA (mtDNA) defects in the pathogenesis of many human and some canine tumours. The aim of this study was to identify mutations in the ND2 and ND4 mitochondrial genes in canine mast cell tumours and determine their association with the process of neoplastic transformation and the phenotypic traits of dogs. In total, 136 gene sequences from 68 biological samples, including blood and neoplastic tissue samples from 34 dogs with diagnosed MCTs, were analysed. The study consisted in DNA sequencing of the ND2 and ND4 genes as well as bioinformatics and statistical analyses. For the first time, mutations in NADH-dehydrogenase genes were detected in dogs with MCTs. In total, 22 polymorphic loci and 19 mutations in the ND2 and ND4 genes were identified. The majority of the identified mutations were homoplasmic, and tumour heteroplasmy was detected in eight nucleotide positions in three dogs. Seven of the ND2 mutations and two of the ND4 mutations caused an amino acid change. The changes in non-synonymous protein-coding SNPs did not exert an adverse effect on proteins. A statistically significant correlation of the presence of mutations/polymorphisms with the sex, age, and size of the dogs and the tumour location was demonstrated. Polymorphisms and mutations in NADH-dehydrogenase genes, including mastocyte-specific changes, in canine mast cell tumours that had not been reported earlier in the literature were identified. Some of these changes may imply that these are the hotspot mutations in canine mast cell tumours. It cannot be excluded that the molecular changes are directly associated with the development of mast cell tumours, and further investigations are needed to verify whether they can become molecular markers of MCTs in the future.

中文翻译：

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犬肥大细胞肿瘤线粒体NADH脱氢酶基因缺陷

摘要 最近的研究表明，线粒体 DNA (mtDNA) 缺陷在许多人类和某些犬肿瘤的发病机制中起着重要作用。本研究的目的是鉴定犬肥大细胞肿瘤中 ND2 和 ND4 线粒体基因的突变，并确定它们与肿瘤转化过程和狗的表型特征的关联。总共分析了来自 68 个生物样本的 136 个基因序列，包括来自 34 只诊断为 MCT 的狗的血液和肿瘤组织样本。该研究包括 ND2 和 ND4 基因的 DNA 测序以及生物信息学和统计分析。首次在患有 MCT 的狗中检测到 NADH 脱氢酶基因的突变。总共鉴定了 ND2 和 ND4 基因中的 22 个多态性位点和 19 个突变。大多数鉴定的突变是同质的，在三只狗的八个核苷酸位置检测到肿瘤异质性。七个 ND2 突变和两个 ND4 突变导致氨基酸变化。非同义蛋白质编码 SNP 的变化不会对蛋白质产生不利影响。证明了突变/多态性的存在与狗的性别、年龄和大小以及肿瘤位置之间的统计学显着相关性。NADH-脱氢酶基因的多态性和突变，包括早期文献中未报道的犬肥大细胞肿瘤中的肥大细胞特异性变化。其中一些变化可能意味着这些是犬肥大细胞肿瘤中的热点突变。