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Mitochondria are eukaryotic organelles that are involved in many metabolic pathways. These organelles play a major role in the process of oxidative phosphorylation (OXPHOS) and apoptosis. Genetic changes in mtDNA may disrupt these processes and lead to abnormal cell function. Abnormalities in nucleotide sequence,of mitochondrial DNA are identified as being characteristics of malignant cells. Changes observed in mtDNA can occur in the early stage of carcinogenesis. Until now, no specific mutations for type of tumor have been found in mitochondrial DNA. After many years of research of mtDNA mutations in malignant transformation, it is still not clear whether mutations present in mitochondrial DNA are primary in relation to a cancer or secondary acquired during carcinogenesis. Disclosure of mutations after a long period of occurrence (when mutated gene occurs predominantly) and slowly progressive nature of symptoms may indicate a primary character of these mutations. Despite intensive studies, the impact of mitochondria on carcinogenesis process is still not clear. Continuation of studies on relationship between mutations of mtDNA and occurrence of cancers can become the basis for identification of prognostic and diagnostic markers for early detection of malignant transformation process and development of new methods of treatments for both humans and dogs. The results of study on oncogenomics of dog, as a model animal, can be employed in the future in human medicine.
Over the past few years, there has been a significant progress in genetic testing in dogs through the development of genomic maps, which make it possible to determine the background of polygenic genetic diseases. The information obtained by mapping the canine genome, a detailed marker map, and the understanding of genome architecture have changed the possibilities and direction of canine genetic research. It is now possible to understand the genomics of the qualitative and quantitative traits associated with the phenotype, genetic predisposition, and genetic background of canine defects and diseases. Investigations of canine genetic diseases are particularly valuable because their results can be used in human medicine. From the medical point of view, genetic diseases in both humans and dogs are similar, which makes it possible to test new therapeutic approaches in the case of orthologous genes containing mutations responsible for genetic disorders.
The aim of this study was to identify mutations in the D-loop region of mtDNA in head, neck, and limb tumours in dogs, and determination of their relationship with the process of neoplastic transformation. Blood and tumour tissue samples from 19 dogs with diagnosed sporadic malignant tumours were analysed. DNA extraction, amplification, and sequencing of the mtDNA D-loop, and bioinformatic analyses were performed. Five mutations and 19 polymorphisms were observed in 68.42% of all tumours. Polymorphic variants were noted in 42.86% of the head and neck tumours and in 58.33% of the limb tumours. Mutations were observed in 21.05% of dogs. The mutations were found in 28.57% of the head and neck tumours and in 16.66% of the limb tumours. The mutations were identified in 50% of the studied epithelial cancers. In the mesenchy mal tumours, no mutations in the D-loop region were observed. Mitochondrial haplotype A17 was found in over 40% cases of limb tumours. No association between the age, breed, sex, type of tumour, and detected polymorphic variants were observed. Different mutational changes in the D-loop sequences of mtDNA identified in the blood and tumour tissues may indicate a relationship between the type of tumour and individual changes in the D-loop nucleotide sequences of mtDNA.
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