Mitochondrial genome aberrations in canine spleen tumours*

The majority of spleen tumours (STs) in dogs are malignant neoplasms with a poor prognosis. To understand the molecular basis of the disease, a number of papers on nuclear DNA (nDNA) have been published in recent years. However, the presented results still do not explain the commonness and aggressive course of STs. In the case of canine spleen neoplasms, the impact of the alterations on mitochondrial DNA (mtDNA) is completely unknown. Therefore, the aim of this study was to identify mtDNA variants based on whole mitochondrial genome sequences obtained from dogs diagnosed with spleen tumours with special regard to haemangiosarcomas (HSA). Samples of blood, tumour, and healthy tissue were collected from animals, and mtDNAs (ultimately 57 samples) were subsequently sequenced. Based on obtained molecular variants, protein analyses were performed for non-synonymous changes. The total number of observed alterations included 1011 SNPs, 20 mutations, 45 indels, 10 indel mutations, and 37 heteroplasmic sites. The highest number of mtDNA variants in protein-coding genes was observed in the COX1, COX3, ND4, ND5, ND1, and ATP6 genes. Most of the identified mtDNA defects were synonymous changes at the amino acid level. In the non-coding region, the highest number of polymorphisms was observed in the hypervariable region I (HVI), and heteroplasmic sites were commonly identified in the variable number tandem repeat (VNTR) region, especially in its fragment spanning 16,148–16,418 bp. The analyses indicate nine SNPs that occurred in all the samples. The total number of mtDNA changes varied from 26 to 123 between the animals. However, if the variants occurred first in 12s rRNA and 16s rRNA, an increased number of mtDNA alterations were observed in the canine mtDNA genome (from 55 to 123).