Imatinib Responsiveness in Canine Mast Cell Tumors Carrying Novel Mutations of <i>c-KIT</i> Exon 11

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  • NAKANO Yuko
    Japan Small Animal Cancer Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan Division of Clinical Epidemiology, Research Center for Medical Science, Jikei University School of Medicine, 3–25–8 Nishi-Shinbashi, Minato-Ku, Tokyo 105–8461, Japan
  • KOBAYASHI Tetsuya
    Japan Small Animal Cancer Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan
  • OSHIMA Fukiko
    Japan Small Animal Cancer Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan
  • FUKAZAWA Eri
    Japan Small Animal Cancer Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan
  • YAMAGAMI Tetsushi
    Japan Small Animal Medical Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan
  • SHIRAISHI Yozo
    Japan Small Animal Medical Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan
  • TAKANOSU Masamine
    Japan Small Animal Medical Center, 2–27–4 Nakatomi-minami, Tokorozawa, Saitama 359–0003, Japan Nasunogahara Animal Clinic, 2–3574–98 Asaka, Ohtawara, Tochigi 324–0043, Japan

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  • Imatinib Responsiveness in Canine Mast Cell Tumors Carrying Novel Mutations of c-KIT Exon 11

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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.

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