Concordance of mutational status in matched primary and metastatic canine dermal mast cell tumors: possible implications for clinical practice

Introduction In dogs, 9-30% of mast cell tumors (MCTs) show mutations in the proto-oncogene c-Kit, and the relevance of mutational status for therapy with tyrosine kinase inhibitors (TKIs) is nowadays accepted. Although TKIs-based therapy is used in dogs with MCTs also to treat nodal metastatic disease, little is known on c-Kit mutational status in metastatic MCTs. In the present study, the occurrence of c-Kit mutations was investigated in matched primary and metastatic MCTs, to make a recommendation on the use of mutational analysis and TKI in the clinical setting. Methods Total RNA or DNA was extracted from primary tumors and corresponding metastases in dogs with histologically-confirmed dermal MCT. Exons 8, 9 and 11 were amplified by PCR and sequenced. Results Eighteen dogs were enrolled, but mutation analysis was carried out in both the primary tumor and corresponding metastases in 13 cases only. Three new mutations were identified: one insertion/deletion in exon 8 (1262_1289delinsTGACTTTCAT), and two internal tandem duplications (ITDs) in exon 11 (amino acids ITD571-582 and ITD574-587). A total concordance in the pattern of c-Kit (mutated or wild type) was noticed between the primary tumor and related metastases. Conclusion Despite the low case load, presented data suggest that c-Kit mutational status is conserved in primary MCT and concurrent lymph node metastases. Thus, both may be used for c-Kit mutational testing. This may have some consequences on clinical decision-making about TKIs therapeutic use. Further confirmatory studies are needed, including those aiming to assess the c-Kit mutational status in metastases other than the lymph node.