title: Detection of novel polymorphisms in the ckit gene of canine patients with lymphoma, melanoma, haemangiosarcoma, and osteosarcoma.
abstract: Tyrosine kinase inhibitors (TKIs) that specifically target cKIT represent a therapeutic approach for non-resectable canine mast cell tumours (MCTs) grade II/III. The therapeutic benefit of TKIs has been investigated in other tumours based on clinical response rates and identification of gain-of-function mutations. In the present study, cKIT expression in 14 dogs with osteosarcoma, melanoma, haemangiosarcoma, lymphoma, and fibrosarcoma was analysed. Tissue samples were used for cKIT sequencing to (I) detect the cKIT transcript and to (II) identify gain-of-function mutations. The cKIT transcript was detected in ten patients. Four novel amino acid substitutions and five silent polymorphisms were identified. Furthermore, an insertion mutation (GNSK) was discovered in the tissue, but not in the blood sample of one dog. CKIT expression was identified in a variety of canine tumours and, therefore, TKIs might have a broader therapeutic indication apart from treatment of MCTs. Further investigations will be necessary to localize the cKIT protein in the respective tumours and to evaluate the functional consequence of the cKIT variants identified in the present study.
authors.affiliation: Small Animal Teaching Hospital, Leahurst Campus, University of Liverpool, Neston, CH64 7TE, United Kingdom. gramer.irina@gmail.com.|Institute of Pharmacology and Toxicology, Justus Liebig University of Giessen, Schubertstr. 81, 35392, Giessen, Germany. gramer.irina@gmail.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Gramer
authors.affiliation: Hofheim Small Animal Clinic, Im Langgewann 9, 65719, Hofheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kessler
authors.affiliation: Institute of Pharmacology and Toxicology, Justus Liebig University of Giessen, Schubertstr. 81, 35392, Giessen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Geyer
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D004283:Dog Diseases / Q000201:enzymology* / Q000235:genetics*; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006394:Hemangiosarcoma / Q000662:veterinary; D008223:Lymphoma / Q000662:veterinary; D008297:Male; D008545:Melanoma / Q000662:veterinary; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D012516:Osteosarcoma / Q000662:veterinary; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D011505:Protein-Tyrosine Kinases
keywords: Dog; Insertion mutation; Polymorphisms; Tumour; Tyrosine Kinase Inhibitors; cKIT