Evaluation of the tRNA-Leu (UUR) gene haplotype profile observed in canine mammary gland tumours based on comparative analysis with the MT-TL1 human gene

Abstract

The aetiology and pathogenesis of many canine tumours are likely to be similar to cancers found in humans. This study aimed to evaluate a plausible link between changes in the tRNA-Leu (UUR) gene and the carcinogenesis process in dogs with mammary gland tumours. The whole mitochondrial DNA (mtDNA) isolated from blood and tumour tissues of 13 dogs with malignant mammary gland tumours was sequenced. The present work is the first report showing that some polymorphisms might occur at the corresponding positions in the human and canine mtDNA genome, which in turn may provoke similar deleterious effects. The homology between the human MT-TL1 and canine tRNA-Leu (UUR) genes was 84%. After resequencing of the whole mitochondrial DNA genome with the use of the NGS technology, two polymorphisms in two haplotypes were identified: m.2683G>A (observed in 18 out of 27 samples) and m.2678_2679insG (27 out of 27 samples). The m.2683G>A polymorphism corresponded to a deleterious change at m.3243A>G, which is linked with MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes) syndrome and with different types of cancers in humans as well. The comparative analysis of MT-TL1 and tRNA-Leu (UUR) led us to hypothesise that the m.2678_2679insG and m.2683G>A polymorphisms might influence the dog’s condition and might be linked with tumourigenesis, as observed in humans.

Mutations and polymorphisms in mitochondrial genome of dogs with solid mammary carcinoma – a preliminary study

“…However, in the present study, changes in the tRNA-Leu (UUR) gene were found in both animals (polymorphism m.2678_79insG in both dogs, mutation m.2683G>A in dog S08, and polymorphism m.5367C>T in dog B114). It is worth noting that a study conducted by Kowal et al in 2022 revealed the aforementioned polymorphism in all 27 samples examined (from dogs with mammary gland tumors) and substitution m.2683G>A in 18, that is, almost 67% of all samples (20). This suggests a possible link between these changes and the process of carcinogenesis in dogs.…”