Imatinib responsiveness in canine mast cell tumors carrying novel mutations of c-KIT exon 11

J Vet Med Sci. 2014 Apr;76(4):545-8. doi: 10.1292/jvms.13-0156. Epub 2013 Nov 29.

Abstract

In 2 individual cases of canine mast cell tumors, we identified 2 novel c-KIT mutations in exon 11: a 9-base pair (bp) deletion (c.1663-1671del) and a point mutation (c.1676T>A). The 9-bp deletion mutation caused a loss of 3 amino acids, corresponding to p.Gln555_Lys557del, and the point mutation resulted in the substitution of valine by aspartic acid (p.Val559Asp) in the juxtamembrane domain of the protein. Imatinib mesylate, a therapeutic agent for canine mast cell tumors, was used to treat both tumors. Complete remission was achieved at 33 and 14 days after administration, respectively. However, in both cases, the therapeutic response subsequently tapered with the duration of remission lasting 66 and 255 days, respectively. Although these 2 novel c-KIT mutations in exon 11 were not confirmed to be gain-of-function mutations, a further study may help clarify relevance between mutations identified in this report and responsiveness.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Benzamides / therapeutic use*
  • Dog Diseases / drug therapy*
  • Dog Diseases / genetics*
  • Dogs
  • Female
  • Gene Components
  • Imatinib Mesylate
  • Lymphatic Metastasis
  • Male
  • Mastocytosis / drug therapy
  • Mastocytosis / genetics
  • Mastocytosis / veterinary*
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Piperazines / therapeutic use*
  • Polymerase Chain Reaction / veterinary
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / therapeutic use*
  • Sequence Analysis, DNA / veterinary
  • Sequence Deletion / genetics
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit