Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs

Sue Downing, May B. Chien, Philip H Kass, Peter F Moore, Cheryl A. London

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Abstract

Objective - To determine the prevalence of activating internal tandem duplications (ITDs) in exons 11 and 12 of c-kit in mast cell tumors (MCTs) of dogs and to correlate these mutations with prognosis. Sample Population - 157 formalin-fixed, paraffin-embedded MCTs from dogs in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis. Procedure - Genomic DNA was isolated from tumor specimens and a polymerase chain reaction procedure was performed to determine whether there were ITDs in exons 11 and 12. Results - We identified ITDs in 1 of 12 (8%) grade-I, 42 of 119 (35%) grade-II, and 9 of 26 (35%) grade-III tumors (overall prevalence, 52 of 157 [33%]). Logistic regression analysis revealed that the odds of grade-II and -III tumors possessing an ITD were approximately 5 times greater than that for graded tumors, although these odds did not differ significantly. Although MCTs possessing an ITD were twice as likely to recur after excision and twice as likely to result in metastasis as those without an ITD, these values also did not differ significantly. Conclusions and Clinical Relevance - These results provide evidence that ITDs in c-kit occur frequently in MCTs of dogs. The high prevalence of c-kit activating mutations in MCTs of dogs combined with the relative abundance of mast cell disease in dogs provide an ideal naturally developing tumor in which to test the safety and efficacy of novel small-molecule kinase inhibitors such as imatinib mesylate.

Original languageEnglish (US)
Pages (from-to)1718-1723
Number of pages6
JournalAmerican Journal of Veterinary Research
Volume63
Issue number12
StatePublished - Dec 1 2002

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mast cells
Mast Cells
exons
Exons
Dogs
neoplasms
dogs
Neoplasms
Veterinary Pathology
Mastocytosis
mutation
Mutation
dog diseases
formalin
Teaching Hospitals
metastasis
Paraffin
alkanes
Formaldehyde
prognosis

ASJC Scopus subject areas

  • veterinary(all)

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Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. / Downing, Sue; Chien, May B.; Kass, Philip H; Moore, Peter F; London, Cheryl A.

In: American Journal of Veterinary Research, Vol. 63, No. 12, 01.12.2002, p. 1718-1723.

Research output: Contribution to journalArticle

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