Mitochondrial D-loop mutations and polymorphisms are connected with canine malignant cancers

Abstract

The aim of the conducted investigations was to identify differences in the D-loop nucleotide sequence between neoplastic tissue, normal tissue, and blood and to determine their correlation with the type of cancer in dogs. In 62.5% of the analyzed tumors of epithelial origin and 25% tumors of mesenchymal origin, substitution was detected within the D-loop sequence between the neoplastic tissue, normal tissue, and blood. Two mutations occurring in the carcinogenic process in position T15620C have been identified in epithelioma glandulae sebacei and carcinoma planoepithelialae keratodes. Blood and cancer heteroplasmy was diagnosed for carcinoma planoepithelialae keratodes and "Comedo" carcinoma. The results of the study indicate that polymorphic changes in the D-loop sequence promote carcinogenesis in dogs. Heteroplasmy diagnosed in blood and tumor cells and absence thereof in normal tissue may imply mtDNA recombination. High prevalence of mtDNA mutations in canine tumors may suggest mtDNA genetic instability, which is likely to play a role in carcinogenesis.

Mitochondrial D-loop mutations can be detected in sporadic malignant tumours in dogs

“…Previous studies concerned mainly mutations in human mtDNA in carcinogenesis (7,11,12,34). Only a few authors have conducted investigations on the relationship between mutations and carcinogenesis process in dogs (3,22,28,29).…”

“…Analysis of mitochondrial DNA (mtDNA) sequences plays an important role in the studies on population genetics and in medicine, including veterinary medicine (7,11,12,(27)(28)(29)32). Results published in the recent years have indicated the prevalence of mitochondrial DNA mutations in tumour cells, which suggests that they may be cancer-causing agents (7,11,12,28,29,32,34).…”

“…Results published in the recent years have indicated the prevalence of mitochondrial DNA mutations in tumour cells, which suggests that they may be cancer-causing agents (7,11,12,28,29,32,34). Up till now, there has been not stated whether the observed changes in mitochondrial DNA result from the development of tumour or are connected with the process of neoplastic transformation (7,11,12,28,29). GrzybowskaSzatkowska and Slaska (12) report the presence of homological changes in the sequence of mtDNA in breast cancer and some mitochondrial diseases, which indicates that mutations in mtDNA in breast cancer may affect the cell and cause its dysfunction, as in the case of mitochondrial diseases.…”

“…The studies on tumour tissues showed a significant number of somatic mutations in mtDNA (3,7,11,12,22,28,29), especially in the D-loop region which controls replication and transcription of mitochondrial DNA. These mutations can lead to disorders in these processes and cell energy functions (7,11,17).…”

“…Somatic mutations in mtDNA have been described in many types of human tumour cells (7, 8, 11-13, 17, 20, 21, 34), but there are only a few literature reports documenting the occurrence of mutations in the mtDNA of dogs with tumours (3,22,28,29,32). Mutations may occur in the entire mitochondrial genome but, most often, they occur in the hypervariable regions of the D-loop (3,22,28,29,32). Therefore, an attempt is made to identify mutations in the mitochondrial D-loop and connect them with the process of carcinogenesis in dogs.…”