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

Open access

Abstract

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 mesenchymal 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.

1. Altschul S.F., Madden T.L., Schäffer A.A., Zhang J., Zhang Z., Miller W., Lipman D.J.: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25, 3389-3402.

2. Asch B. Van, Albarran C., Alonso A., Angulo R., Alves C., Betancor E., Catanesi C.I., Corach D., Crespillo M., Doutremepuich C., Estonba A., Fernandes A.T., Fernandez E., Garcia A.M., Garcia M.A., Gilardi P., Goncalves R., Hernandez A., Lima G., Nascimento E., de Pancorbo M.M., Parra D., Pinheiro M.F., Prat E., Puente J., Ramirez J.L., Rendo F., Rey I.D.R.F., Rodriguez A., Sala A., Salla J., Sanchez J.J., Sola D., Silva S., Pestano Brito J.J., Amorim A.: Forensic analysis of dog (Canis lupus familiaris) mitochondrial DNA sequences: an inter-laboratory study of the GEP-ISFG working group. Forensic Sci Int Genet 2009, 4, 49-54.

3. Bertagnolli A.C., Sores P., Van Asch B., Amorim A., Cirnes L., Maximo V., Cassali G.D.: An assessment of the clonality of the components of canine mixed mammary tumors by mitochondrial DNA analysis. Vet J 2009, 182, 269-274.

4. Brønden L.B., Eriksen T., Kristenes A.T.: Oral malignant melanomas and other head and neck neoplasms in Danish dogsdata from the Danish Veterinary Cancer Registry. Acta Vet Scand 2009, 18, 51-54.

5. Carew J.S., Huang P.: Mitochondrial defects in cancer. Mol Cancer. 2002, 1, 9.

6. Challen C., Brown H., Cai C., Betts G., Peterson I., Sloan P., West C., Birch-Machin M., Robinson M.: Mitochondrial DNA mutations in head and neck cancer are infrequent and lack prognostic utility. Br J Cancer 2011, 104, 1319-1324.

7. Czarnecka A.M., Golik P., Bartnik E.: Mitochondrial DNA mutations in human neoplasia. J Appl Genet 2006, 47, 67-78.

8. D'Aurelio M., Gajewski C.D., Lin M.T., Mauck W.M., Shao L.Z., Lenaz G., Moraes C.T., Manfredi G.: Heterologous mitochondrial DNA recombination in human cells. Hum Mol Genet 2004, 13, 3171-3179.

9. DNA Baser Sequence Assembler v3.2. Heracle BioSoft SRL Romania. 2012. Available at: http://www.DnaBaser.com

10. Dobson J.M.: Breed-predispositions to cancer in “pedigree dogs”. ISRN Vet Sci 2013, doi: 10.1155/2013/941275.

11. Grzybowska-Szatkowska L., Slaska B.: Mitochondrial DNA and carcinogenesis (Review). Mol Med Rep 2012, 6, 923-930.

12. Grzybowska-Szatkowska L., Slaska B.: Mitochondrial NADH- dehydrogenase polymorphisms are associated with breast cancer in Poland. J Appl Genet 2014, doi: 10.1007/s13353-013-0190-9.

13. Guo W., Yang D., Xu H., Zhang Y., Huang J., Yang Z., Chen X., Huang Z.: Mutations in the D-loop region and increased copy number of mitochondrial DNA in human laryngeal squamous cell carcinoma. Mol Biol Rep 2013, 40, 13-20.

14. Huang X., Madan A.: CAP3: A DNA sequence assembly program. Genome Res 1999, 9, 868-77.

15. Imes D.L., Wictum E.J., Allard M.W., Sacks, B.N.: Identification of single nucleotide polymorphisms within the mtDNA genome of the domestic dog to discriminate individuals with common HVI haplotypes. Forensic Sci Int Genet 2012, 6, 630-639.

16. Kim K.S., Lee S.E., Jeong H.W., Ha J.H.: The complete nucleotide sequence of the domestic dog (Canis familiaris) mitochondrial genome. Mol Phylogenet Evol 1998, 10, 210-220.

17. Kohler C., Radpour R., Barekati Z., Asadollahi R., Bitzer J., Wight E., Bürki N., Diesch C., Holzgreve W., Zhong X.Y.: Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. Mol Cancer 2009, 8, 115.

18. Król M., Motyl T.: Exploiting cancer genomics in pet animals to gain advantage for personalized medicine decisions. J Appl Genet 2014, 55, 337-341.

19. Król M., Pawłowski K.M., Motyl T.: DNA microarrays in veterinary oncology. Med Weter 2009, 65, 377-380.

20. Lin S.A., Jiang R.S., Chen F.J., Wang W.Y., Lin J.C.: Somatic mutations in the D-loop of mitochondrial DNA in oral squamous cell carcinoma. Eur Arch of Oto-Rhino-L 2012, 29, 1665-1670.

21. Lièvre A., Blons H., Houllier A.M., Laccourreye O., Brasnu D., Beaune P., Laurnet-Puig P.: Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma. Br J Cancer 2006, 94, 692-697.

22. Murgia C., Pritchard J., Kim S.Y., Fassati A., Weiss R.A.: Clonal origin and evolution of transmissible cancer cell 2006, 126, 478-488.

23. Pereira L., Van Asch B., Amorim A.: Standardisation of nomenclature for dog mtDNA D-loop: a prerequisite for launching a Canis familiaris database. Forensic Sci Int 2004, 141, 99-108.

24. Rivera P., von Euler H.: Molecular biological aspects of canine and human mammary tumors. Vet Pathol 2011, 48, 132-146.

25. Rowell J.L., McCarthy D.O., Alvarez C.E.: Dog models of naturally occurring cancer. Trends Mol Med 2011, 17, 380-388.

26. Savolainen P., Zhang Y.P., Luo J., Lundeberg J., Leitner T.: Genetic evidence for an East Asian origin of domestic dogs. Science 2002, 298, 1610-1613.

27. Slaska B., Grzybowska-Szatkowska L.: Analysis of the mitochondrial haplogroups of farm and wild-living raccoon dogs in Poland. Mitochondrial DNA 2011, 22, 105-110.

28. Slaska B., Grzybowska-Szatkowska L., Nisztuk S., Surdyka M., Rozanska D.: Mitochondrial DNA polymorphism in genes encoding ND1, COI and CYTB in canine malignant cancers. Mitochondrial DNA 2013, doi: 10.3109/19401736.2013.840594.

29. Slaska B., Grzybowska-Szatkowska L., Surdyka M., Nisztuk S., Rozanska D., Rozanski P., Smiech A., Orzelski M.: Mitochondrial D-loop mutations and polymorphisms are connected with canine malignant cancers. Mitochondrial DNA 2013, doi: 10.3109/19401736.2013. 792054.

30. Sobczyńska-Rak A., Silmanowicz P., Piórkowski J., Polkowska I., Dębiak P.: Selected oral cavity tumors in dogs. Med Weter 2005, 61, 66-69.

31. Switonski M.: Dog as a model in studies on human hereditary diseases and their gene therapy. Reprod Biol 2014, 14, 44-50.

32. Ślaska B., Grzybowska-Szatkowska L., Bugno-Poniewierska M., Surdyka M., Śmiech A.: Nuclear and mitochondria DNA mutation in human and canine tumors. Med Weter 2013, 69, 195-202.

33. Świtoński M.: Gene mutations causing hereditary diseases in dogs. Anim Sci Pap Rep 2004, 22, 131-134.

34. Wallace D.C.: A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Ann Rev Genet 2005, 39, 359-407.

35. Zań R., Roliński Z., Kowalski C., Burmańczuk A.: Melatonin, a potential new anticancer drug in animals. Med Weter 2012, 68, 343-348.

Bulletin of the Veterinary Institute in Pulawy

The Journal of National Veterinary Research Institute in Pulawy

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