Might canine mast cell tumors share some molecular pathways with human systemic mastocytosis besides c-KIT?

Introduction Human systemic mastocytosis (SM) and canine cutaneous mast cell tumor (MCT) are both characterized by proliferation and the accumulation of abnormal mast cells in tissues and the presence of activating mutations in the receptor tyrosine kinase c-KIT. Recently, it has been shown that additional cooperating events are likely to contribute to SM pathogenesis and/or phenotype. In present study, hypothesizing analogies in molecular mechanisms and gene dysfunctions between SM and canine MCT, the mutational profile of some genes, commonly mutated in human myeloid malignancies and involved in splicing machinery, DNA methylation and signal transduction processes, was investigated in canine MCTs. Materials and Methods Genomic DNA was extracted from 75 MCT biopsies. Canine TET2, IDH2, IDH1, SRSF2, SF3B1, KRAS and NRAS DNA sequences were identified and the presence of “human-like” hot spot mutations was checked by using a ABI 3730 sequencer. Results No mutations were ever identified in target genes except for TET2, for which one point-mutation and one amino-acid deletion, detected in 2 samples (3.7%), and a single nucleotide polymorphism (SNP) found out in TET2 exon 11 (a tandem repetition of a glutamine amino-acid). Conclusion In SM, TET2 mutations occur at a frequency ten times higher than the one observed in the dog. Therefore, it looks like that the two pathologies might differ in molecular pathways involved in the disease pathogenesis; despite this, the TET2 tandem SNP is actually under investigation in a population of healthy dogs to verify any predisposition in disease development.