title: Imatinib responsiveness in canine mast cell tumors carrying novel mutations of c-KIT exon 11.
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.
authors.affiliation: Japan Small Animal Cancer Center, 2-27-4 Nakatomi-minami, Tokorozawa, Saitama 359-0003, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Fukiko
authors.initials: F
authors.lastname: Oshima
authors.forename: Eri
authors.initials: E
authors.lastname: Fukazawa
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yamagami
authors.forename: Yozo
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Masamine
authors.initials: M
authors.lastname: Takanosu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001549:Benzamides / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics*; D004285:Dogs; D005260:Female; D040461:Gene Components; D000068877:Imatinib Mesylate; D008207:Lymphatic Metastasis; D008297:Male; D008415:Mastocytosis / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA / Q000662:veterinary; D017384:Sequence Deletion / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit