Detection of Mutations in Selected Proto-Oncogenes of Canine Lymphoma

G. Bóna 1  and K. Šiviková 1
  • 1 Department of Biology and Genetics, Institute of Genetics, University of Veterinary Medicine and Pharmacy, , Košice, Slovakia

Abstract

Lymphomas belong among the most frequently diagnosed tumours of the haematopoietic system in dogs. The clinical manifestations and genetic and molecular basis of canine lymphoma resembles those of human non-Hodgkin lymphoma and therefore it can serve as a suitable model for the study of this disease. Neoplastic diseases are the consequence of a number of genetic and epigenetic changes in somatic cells. One of such changes are gene mutations that can subsequently cause changes in the activity of proto-oncogenes and tumour suppressor genes. The aim of our study was to detect potential mutations in selected exons of proto-oncogenes in DNA isolated from samples of lymphoma obtained from two donors - a Bernese Mountain Dog and a female mongrel. On the basis of literary data descriptions of human and canine haematopoietic neoplastic diseases, our investigations of potential changes in DNA focused on proto- oncogenes C-KIT - exons 8, 17; NRAS - exons 1, 2;FLT3 - exons 14, 15 and 20. The investigated samples were amplified by polymerase chain reaction (PCR) and subjected to sequencing. The DNA sequences were compared with reference sequences in the database Ensembl. The comparison of sequences of the C-KIT gene revealed an A/G transition at the 35th nucleotide of exon 8 in the mongrel. It involved a synonymous exchange of the nucleotide in the codon that did not cause a change in the amino acid. In the same sample we recorded several point mutations in the intron regions surrounding the exons 14 and 20 of the FLT3 gene. Changes in the intron regions can affect the expression of genes and thus can play an important role in the origin and development of tumours. No genetic mutations were detected in any gene regions of the Bernese Mountain Dog. In the case of the NRAS gene, no changes were observed in any sample collected from the donors.

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  • 1. Devita, V. T., Lawrence, T. S., Rosenberg, S. A., 2015: Cancer: Principles and Practice of Oncology, 10th edn., Lippincott Williams and Wilkins, 2234 pp.

  • 2. Edwards, M. D., Pazzi, K. A., Gumerlock, P. H., 1993: cNras is activated infrequently in canine malignant lymphoma. Toxicol. Pathol., 21, 288-291.

  • 3. Giantin, M., Aresu, L., Aricò, A., Gelain, M. E., Riondato, F., Comazzi. S. et al., 2013: Evaluation of tyrosine-kinase receptor c-kit mutations, mRNA and protein expression in canine lymphoma: Might c-kit represent a therapeutic target ? Vet. Immunol. Immunopathol., 154, 153-159.

  • 4. Chorev, M., Carmel, L., 2012: The function of introns. Frontiers in genetics, 3, 1-15.

  • 5. Ito, D., Frantz, A. M., Modiano, J. F., 2014: Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet. Immunol. Immunopathol., 159, 192-201.

  • 6. London, C. A., Galli, S. J., Yuuki, T., Hu, Z. Q., Helfand, S. C., Geissler, E. N., 1999: Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene ckit. Exp. Hematol., 27, 689-697.

  • 7. Mayr, B., Winkler, G., Schaffner, G., Reifinger, M., Brem, G., 2002: N-ras mutation in a feline lymphoma. Low frequency of N-ras mutations in a series of feline, canine and bovine lymphomas. Vet. J., 163, 326-328.

  • 8. Richter, A., Escobar, H. M., Gunther, K., Soller, J. T., Winkler, S., Nolte, I. et al., 2005: RAS gene hot-spot mutations in canine neoplasias. J. Hered., 96, 764−765.

  • 9. Roman, E., Smith, A. G., 2011: Epidemiology of lymphomas. Histopathology, 58, 4-14.

  • 10. Small, D., 2006: FLT3 mutations: biology and treatment. ASH Education Program Book, 2006, 178-184.

  • 11. Stewart, B. W., Wild, C. P., 2014: World Cancer Report 2014. Lyon, International Agency for Research on Cancer, 630 pp.

  • 12. Suter, S. E., Small, G. W., Seiser, E. L., Thomas, R., Breen, M., Richards, K. L., 2011: FLT3 mutations in canine acute lymphocytic leukemia. BMC cancer, 11, 38.

  • 13. Usher, S. G., Radford, A. D., Villiers, E. J., Blackwood, L., 2009: RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias. Exp. Hematol., 37, 65-77.

  • 14. Valli, E. V., San Myint, M., Barthel, A., Bienzle, D., Caswell, J., Colbatzky, F. et al., 2011: Classification of canine malignant lymphomas according to the World Health Organization criteria. Vet. Pathol., 48, 198-211.

  • 15. Weinberg, R., 2013: The Biology of Cancer. Garland Science, 876 pp.

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