Imatinib Responsiveness in Canine Mast Cell Tumors Carrying Novel Mutations of c-KIT Exon 11
نویسندگان
چکیده
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.
منابع مشابه
Mutations in C-KIT exon 11 in canine cutaneous mast cell tumors
Background The c-KIT proto-oncogene encodes the receptor tyrosine kinase KIT, which has been shown to play important roles in the cellular maturation, survival, proliferation, and migration of several cell types including mast cells. Mast cell tumors (MCTs) are the most common cutaneous tumor in the dog. MCTs exhibit wide variation in biological behavior. KIT mutations and aberrant KIT expressi...
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Activating mutations in the receptor tyrosine kinase, c-KIT,were first described by Furitsu and colleagues (1) in a variant of the human mast cell line, HMC1. Two missense mutations resulting in single amino acid changes were observed: one in exon 11 leading to a V560G substitution in the intracellular juxtamembrane region, and the other in exon 17 causing a D816V substitution in the activation...
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