title: Evaluation of tyrosine-kinase receptor c-kit mutations, mRNA and protein expression in canine lymphoma: might c-kit represent a therapeutic target?
abstract: c-kit plays an important role in proliferation, survival and differentiation of hematopoietic progenitor cells. In human hematopoietic malignancies, c-kit is mostly expressed by progenitor cell neoplasms and seldom by mature cell neoplasms. Aim of this study was to evaluate c-kit expression in canine lymphoma. Twenty-five B-cell lymphomas and 21 T-cell lymphomas were enrolled in the study. c-kit mRNA and protein expression was measured in lymph node fine needle aspirates by quantitative real-time RT-PCR, flow cytometry and immunocytochemistry, while the occurrence of KIT mutations on exons 8-11 and 17 was investigated by direct cDNA sequencing. KIT mRNA was amplifiable but below the limit of quantification in 76% of B-cell lymphomas and 33% of T-cell lymphomas. Remaining samples showed a very low expression of KIT, except for some high grade (HG) T-cell lymphomas where a comparatively higher mRNA amount was observed. Transcriptional data were confirmed at the protein level. No gain-of-function mutations were observed. Among canine lymphomas, T-cell lymphoma typically shows an aggressive biological behavior, partly being attributable to the lack of efficacious treatment options, and the evidence of c-kit expression in HG T-cell lymphomas might represent the rationale for its routinely diagnostic evaluation and the use of tyrosine kinase inhibitors in future clinical trials.
authors.affiliation: Dipartimento di Biomedicina Comparata e Alimentazione, Università degli Studi di Padova, viale Università 16, 35020 Agripolis-Legnaro Padova, Italy. mery.giantin@unipd.it
authors.forename: M
authors.initials: M
authors.lastname: Giantin
authors.forename: L
authors.initials: L
authors.lastname: Aresu
authors.forename: A
authors.initials: A
authors.lastname: Aricò
authors.forename: M E
authors.initials: ME
authors.lastname: Gelain
authors.forename: F
authors.initials: F
authors.lastname: Riondato
authors.forename: S
authors.initials: S
authors.lastname: Comazzi
authors.forename: M
authors.initials: M
authors.lastname: Dacasto
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000662:veterinary*; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000662:veterinary*; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit