<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The aim of the study was to find associations between the process of neoplastic transformation and mtDNA mutations/polymorphisms, i.e. factors with potential prognostic significance, and to determine their impact on the biochemical properties, as well as structural, and functional properties of proteins. Blood and neoplastic tissue samples were collected from a 9-year-old Labrador dog with a diagnosed malignant mammary tumour. Next-generation genome sequencing (NGS) of the entire mitochondrial genome was performed using Illumina technology, and bioinformatics analyses were carried out. This is the first report demonstrating the application of NGS in the analysis of the canine mtDNA genome in neoplastic disease. The proposed strategy is innovative and promising. For the first time in the literature, the sequence of 29 genes was analysed to determine their association with the prevalence of tumour. In total, 32 polymorphic loci and 15 mutations were identified. For the first time, as many as 24 polymorphisms and all the mutations have been described to be associated with the neoplastic process in dogs. Most polymorphisms/mutations were found in the D-loop (31% of the polymorphisms and 93% of the mutations) and the <italic>COX1</italic> gene sequence (16% of the polymorphisms). Blood or cancer heteroplasmy was noted in 93% of the mutations. Four of the 18 polymorphisms detected in the protein-coding genes were non-synonymous polymorphisms that have not been described in the literature so far (m.T7593C in <italic>COX2</italic>, m.G8807A in <italic>COX3</italic>, m.A9911G in <italic>ND4L</italic>, and m.T13299A in <italic>ND5</italic>) but resulted in changes in amino acids in proteins. These mutations and polymorphisms can affect mitochondrial functions and may be a result of cell adaptation to the changes in the environment occurring during carcinogenesis. The replacement of “wild type” mtDNA by a mutated molecule may be an important phenomenon accompanying carcinogenesis.</p></abstract>

The aim of the study was to find associations between the process of neoplastic transformation and mtDNA mutations/polymorphisms, i.e. factors with potential prognostic significance, and to determine their impact on the biochemical properties, as well as structural, and functional properties of proteins. Blood and neoplastic tissue samples were collected from a 9-year-old Labrador dog with a diagnosed malignant mammary tumour. Next-generation genome sequencing (NGS) of the entire mitochondrial genome was performed using Illumina technology, and bioinformatics analyses were carried out. This is the first report demonstrating the application of NGS in the analysis of the canine mtDNA genome in neoplastic disease. The proposed strategy is innovative and promising. For the first time in the literature, the sequence of 29 genes was analysed to determine their association with the prevalence of tumour. In total, 32 polymorphic loci and 15 mutations were identified. For the first time, as many as 24 polymorphisms and all the mutations have been described to be associated with the neoplastic process in dogs. Most polymorphisms/mutations were found in the D-loop (31% of the polymorphisms and 93% of the mutations) and the COX1 gene sequence (16% of the polymorphisms). Blood or cancer heteroplasmy was noted in 93% of the mutations. Four of the 18 polymorphisms detected in the protein-coding genes were non-synonymous polymorphisms that have not been described in the literature so far (m.T7593C in COX2, m.G8807A in COX3, m.A9911G in ND4L, and m.T13299A in ND5) but resulted in changes in amino acids in proteins. These mutations and polymorphisms can affect mitochondrial functions and may be a result of cell adaptation to the changes in the environment occurring during carcinogenesis. The replacement of “wild type” mtDNA by a mutated molecule may be an important phenomenon accompanying carcinogenesis.

Analysis of Mitochondrial Genome from Labrador (<italic>Canis lupus familiaris</italic>) with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

Institute of Biological Bases of Animal Production, Faculty of Biology, Animal Sciences and Bioeconomy

Laboratory of DNA Sequencing and Oligonucleotide Synthesis

Sub-Department of Clinical Diagnostic and Veterinary Dermatology, Faculty of Veterinary Medicine

Annals of Animal Science

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Analysis of Mitochondrial Genome from Labrador () with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

The aim of the study was to find associations between the process of neoplastic transformation and mtDNA mutations/polymorphisms, i.e. factors with potential...

Analysis of Mitochondrial Genome from Labrador (Canis lupus familiaris) with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

Online veröffentlicht: 30. Juli 2019

Seitenbereich: 619 - 632

Eingereicht: 24. Jan. 2019

Akzeptiert: 26. März 2019

DOI: https://doi.org/10.2478/aoas-2019-0027

Schlüsselwörter
tumour, dog, mtDNA, mutations, NGS

© 2019 Krzysztof Kowal et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Analysis of Mitochondrial Genome from Labrador (Canis lupus familiaris) with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

Online veröffentlicht: 30. Juli 2019

Seitenbereich: 619 - 632

Eingereicht: 24. Jan. 2019

Akzeptiert: 26. März 2019

DOI: https://doi.org/10.2478/aoas-2019-0027

Schlüsselwörtertumour, dog, mtDNA, mutations, NGS

© 2019 Krzysztof Kowal et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
tumour, dog, mtDNA, mutations, NGS