Detection of c-kit mutations in canine mast cell tumors using the polymerase chain reaction technique
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Published:
Jan 28, 2020
Keywords:
c-kit gene Mast cell tumor Mutation Dog
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Abstract
Twenty-seven dogs with mast cell tumor conducted by the biopsy samples examined by histopathology and four samples from normal dogs which had been treated at Veterinary Teaching Animal Hospital, Kasetsart University were included. The purpose of the study was to identify the mutation pattern of c-kit proto-oncogene of tyrosine kinase that had internal tandem duplications (ITD) in exons 11 and 12 of tumor samples. Tumor DNA was amplified by polymerase chain reaction technique. The affected dogs were > 10 years old (50%), 6-10 years old (35%) and < 6 years old (15%). The tumor site was variable. The commonest site was cutaneous (34%). The mast cell tumor samples were divided into grade I (30 %), grade II (56 %) and grade III (15%). Mutation of the c-kit proto-oncogene was found in two dogs with grade II and III (7.4%) with ITD size of 43 and 52 base pairs. This result indicates c-kit proto-oncogene mutation is uncommon in dogs. Therefore, ITD detection is not a suitable diagnosis for mast cell tumor in dog but may be used as a predictive marker for tumor status especially in higher grade tumor. The drug response has been reported in dogs with the ITD. Therefore this test is useful in the application of the drugs therapy such as imatinib and masitinib that can inhibit the mutation of internal tandem duplications (ITDs) of the c-kit proto-oncogene in the dog that are not suitable for surgery.
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Phavaphutanon, J., Kunakornsawat, S., Prihirunkij, K., Jaidee, A., Laopiem, S., Boonwittaya, N., Niyatiwatchanchai, N., & Sutthiprapa, W. (2020). Detection of c-kit mutations in canine mast cell tumors using the polymerase chain reaction technique. Veterinary Integrative Sciences, 18(1), 1–11. Retrieved from https://he02.tci-thaijo.org/index.php/vis/article/view/236939
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References
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- Reguera, M.J., Ferrer, L., Rabanal, R.M., 2002.. Evaluation of an intron deletion in the c-kit gene of canine mast cell tumors. Am. J. Vet. Res.63:1257-1261.
- Riva, F., Brizzola, S., Stefanello, D., Crema, S., Turin, L., 2005. A study of mutations in the c-kit gene of 32 dogs with mastocytoma. J. Vet. Diagn. Invest. 17: 385-388.
- Roskoski, R. Jr., 2005. Structure and regulation of Kit protein-tyrosine kinase—the stem cell factor receptor, Biochem. Biophys Res. Commun.338:1307-1315.
- Serve, H., Yee, N.S., Stella, G., Sepp-Lorenzino, L., Tan, J.C., Besmer, P., 1995. Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO. J. Feb 1;14(3):473-83.
- Takeuchi, Y., Fujino, Y., Watanabe, M., Takahashi, M., Nakagawa, T., Takeuchi, A. Bonkobara, M., Kobayashi, T., Ohno, K., Uchida, K., Asano, K., Nishimura, R., Nakayama, H., Sugano, S., Ohashi, Y., Tsujimoto, H., 2013. Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumors: A retrospective cohort study. Vete. J.196:492-498.
- Thamm, D.H., Mauldin, E.A.,Vail, D.M., 1999. Prednisone and vinblastine chemotherapy for canine mast cell tumor 41 cases (1992–1997). J. Vet. Intern. Med. 13, 491–497.
- Webster, J.D., Yuzbasiyan-Gurkan, V., Kaneene, J.B., Miller, R.A., Resau, J.H., Kiupel, M., 2006. The role of c-kit in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 8:104-111.
- Webster, J.D, Yuzbasiyan-Gurkan, V., Thamm, D.H., Hamilton, E., Kiupel, M., 2008. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone BMC Vet. Res. 4:32.
- Welle, M.M., Bley, C.R., Howard, J., Rufenacht, S., 2008. Canine mast cell tumors: a review of the pathogenesis, clinical features, pathology and treatment. Vet. Dermatol. 19: 321–339.
- White, C.R., Hohenhaus, A.E., Kelsey, J., Procter-Gray, E. 2011. Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster. J. Am. Anim. Hosp. Assoc. 47: 210–216.
- Yee, N.S., Paek, I., Besmer, P., 1994. Role of kit-ligand in proliferation and suppression of apoptosis in mast cells: basis for radiosensitivity of white spotting and steel mutant mice. J. Exp. Med. 179:1777-1787
- Zemke, D, Yamini, B., Yuzbasiya-Gurkan, V., 2001. Characterization of an undifferenntiated malignancy as a mast cell tumor using mutation analysis in the proto-oncogene c-kit. J. Vet. Diagn. Invest.13:341-345.
- Zemke, D., Yamini, B., Yuzbasiyan-Gurkan, V., 2002. Mutations in the juxtamembrane domai of c-KIT are associated with higher grade mast cell tumors in dogs. Vet. Pathol. 39:529-535.
- Zorzan, E., Hanssens, K., Giantin, M., Dacasto, M., and Dubreuil, P. 2015. Mutational hotspot of TET2, IDH1, IDH2, SRSF2, SF3B1, KRAS, and NRAS from human systemic mastocytosis are not conserved in canine mast cell tumors. PLoS ONE, 10(11), e0142450.
- Zsebo, K.M., Williams, D.A., Geissler, E.N., Broudy, V.C., Martin, F.H., Atkins, H.L., Hsu, R.Y., Birkett, N.C., Okino, K.H., Murdock, D.C., Frederick, W.J., Keith, E.L., Kent, A.S., Takashi, T., Bruce, M.C., Stephen, J.G., Sidney, V.S., 1990. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 633:213-224.
- Broudy, V.C., 1977. Stem cell factor and hematopoiesis. Blood 90:1345–1364.
- Cameron, L.R.J., Robert, A.G., May, B.C., Leslie, A.L., Cheryl A.L., 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent polyacrylamide gel electrophoresis. J. Vet. Diagn. Invest. 16:95-100.
- Chatterjee, A., Joydeep, G., Reuben, K., 2015. Mastocytosis: a mutated KIT receptor induced
myeloproliferative disorder. Oncotarget Jul 30; 6(21): 18250–18264.
- Cheng, T.H., Sheng-Pyng, C., Tzu-Chuan, L., Wen-Chi, C., Jenn-Shing, S., Yi-Shing, S., 2010. Optimal DNA extraction from buccal swab samples. J. Med. Sci. 30(4): 149-154.
- Dagher, R., Cohen, M., Williams, G., Rothmann, M., Gobburu, J., Robbie, G., Rahman, A., Chen, G., Staten, A., Griebel, D., Pazdur., R., 2002. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin. Cancer Res. 8: 3034-3038.
- Dastych, J., Metcalfe, D.D., 1994. Stem cell factor induces mast cell adhesion to fibronectin. J. Immunol. 152:213–219.
- Downing, S., Chien, M.B., Philip, B.S., Kass, H., Moore, P.F., London, C.A., 2002. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c- kit in mast cell tumors of dogs. Am. J. Vet. Res. 63:1718-1723.
- Galli, S.J., Zsebo, K.M., Geissler, E.N., 1994 The kit ligand, stem cell factor. Adv, Immunol. 55:1–96.
- Isotani, M., Ishida, N., Tominaga, M., Tamura, K., Yagihara, H., Ochi, S., Kato, R., Kobayashi, T., Fujita, M., Fujino, Y., Setoguchi, A., Ono, K., Washizu, T., Bonkobara, M., 2008. Effect of Tyrosine Kinase Inhibition by Imatinib Mesylate on Mast Cell Tumors in Dogs. J. Vet. Intern. Med. 22: 985–988.
- Jones, C.L.R., Grahn, R.A., Chien, M.B., Lyons, L.A., London, C.A., 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent polyacrylamide gel electrophoresis. J. Vet. Diag. Invest.16: 95-100.
- Letard, S., Yang, Y., Hanssens, K., Palmérini, F., Leventhal, P.S., Guéry, S., Moussy, A., Kinet, J.P., Hermine, O., Dubreuil, P., 2008. Gain-of-function mutations in the extracellular domain of KIT are common in canine mast cell tumors. Mol. Cancer Res.6:1137–1145.
- London, C.A., Kisseberth, W.C., Galli, S.J., Geissler, E.N., Helfand, S.C., 1996. Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumors. J. Comp. Pathol. Nov;115(4):399-414.
- 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 c-kit. Exp. Hematol. Apr;27(4):689-97.
- London, C.A., Seguin, B., 2003. Mast cell tumors in the dog. Vet. Clin. North. Am. Small Anim. Pract. 33, 473-489 v.
- London, C.A., Thamm D.H, 2013. Mast cell tumors. In: Small animal clinical oncology, Withrow SJ and MacEwen EG, 5thed., Elsevier Saunders, St. Louis, Missouri, pp 335-355.
- Meininger, C.J., Yano, H., Rottapel, R., Bernstein, A., Zsebo, K.M., Zette, B.R., 1992. The c-kit receptor ligand functions as a mast cell chemoattractant. Blood 79: 958-963
- Misdorp, W., 2004. Mast cells and canine mast cell tumors. A review. Vet. Q. Dec;26(4):156-69.
- Nocka, K., Buck, J., Levi, E, Besmer, P., 1990. Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO. J. Oct 9(10): 3287–3294
- Patnaik, A.K., Ehler, W.J., MacEwen, E.G., 1984. Canine Cutaneous Mast Cell Tumor: Morphologic Grading and Survival Time in 83 Dogs. Vet. Pathol. 21:469-474.
- Pryer, N.K., Lee, L.B., Zadovaskaya, R., Yu, X., Sukbuntherng, J., Cherrington, J.M., London, C.A., 2003. Proof of target for SU11654: inhibition of KIT phosphorylation I canine mast cell tumors. Clin. Cancer Res.9:5729-5734.
- Reguera, M.J., Ferrer, L., Rabanal, R.M., 2002.. Evaluation of an intron deletion in the c-kit gene of canine mast cell tumors. Am. J. Vet. Res.63:1257-1261.
- Riva, F., Brizzola, S., Stefanello, D., Crema, S., Turin, L., 2005. A study of mutations in the c-kit gene of 32 dogs with mastocytoma. J. Vet. Diagn. Invest. 17: 385-388.
- Roskoski, R. Jr., 2005. Structure and regulation of Kit protein-tyrosine kinase—the stem cell factor receptor, Biochem. Biophys Res. Commun.338:1307-1315.
- Serve, H., Yee, N.S., Stella, G., Sepp-Lorenzino, L., Tan, J.C., Besmer, P., 1995. Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO. J. Feb 1;14(3):473-83.
- Takeuchi, Y., Fujino, Y., Watanabe, M., Takahashi, M., Nakagawa, T., Takeuchi, A. Bonkobara, M., Kobayashi, T., Ohno, K., Uchida, K., Asano, K., Nishimura, R., Nakayama, H., Sugano, S., Ohashi, Y., Tsujimoto, H., 2013. Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumors: A retrospective cohort study. Vete. J.196:492-498.
- Thamm, D.H., Mauldin, E.A.,Vail, D.M., 1999. Prednisone and vinblastine chemotherapy for canine mast cell tumor 41 cases (1992–1997). J. Vet. Intern. Med. 13, 491–497.
- Webster, J.D., Yuzbasiyan-Gurkan, V., Kaneene, J.B., Miller, R.A., Resau, J.H., Kiupel, M., 2006. The role of c-kit in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 8:104-111.
- Webster, J.D, Yuzbasiyan-Gurkan, V., Thamm, D.H., Hamilton, E., Kiupel, M., 2008. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone BMC Vet. Res. 4:32.
- Welle, M.M., Bley, C.R., Howard, J., Rufenacht, S., 2008. Canine mast cell tumors: a review of the pathogenesis, clinical features, pathology and treatment. Vet. Dermatol. 19: 321–339.
- White, C.R., Hohenhaus, A.E., Kelsey, J., Procter-Gray, E. 2011. Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster. J. Am. Anim. Hosp. Assoc. 47: 210–216.
- Yee, N.S., Paek, I., Besmer, P., 1994. Role of kit-ligand in proliferation and suppression of apoptosis in mast cells: basis for radiosensitivity of white spotting and steel mutant mice. J. Exp. Med. 179:1777-1787
- Zemke, D, Yamini, B., Yuzbasiya-Gurkan, V., 2001. Characterization of an undifferenntiated malignancy as a mast cell tumor using mutation analysis in the proto-oncogene c-kit. J. Vet. Diagn. Invest.13:341-345.
- Zemke, D., Yamini, B., Yuzbasiyan-Gurkan, V., 2002. Mutations in the juxtamembrane domai of c-KIT are associated with higher grade mast cell tumors in dogs. Vet. Pathol. 39:529-535.
- Zorzan, E., Hanssens, K., Giantin, M., Dacasto, M., and Dubreuil, P. 2015. Mutational hotspot of TET2, IDH1, IDH2, SRSF2, SF3B1, KRAS, and NRAS from human systemic mastocytosis are not conserved in canine mast cell tumors. PLoS ONE, 10(11), e0142450.
- Zsebo, K.M., Williams, D.A., Geissler, E.N., Broudy, V.C., Martin, F.H., Atkins, H.L., Hsu, R.Y., Birkett, N.C., Okino, K.H., Murdock, D.C., Frederick, W.J., Keith, E.L., Kent, A.S., Takashi, T., Bruce, M.C., Stephen, J.G., Sidney, V.S., 1990. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 633:213-224.