Transcriptomic analysis identified up-regulation of solute carrier transporters and UDP glucuronosyltransferases in dogs with aggressive cutaneous mast cell tumors.

Introduction: The last decade has witnessed significant advances in personalized treatments as a result of genomic analysis and targeted drug therapies. In the present study, the transcriptome of dogs that had died because of mast cell tumors (MCTs) was characterized to identify a fingerprint having significant influence on cancer risk assessment, prognosis determination and treatment selection. Materials and Methods: The transcriptome of 7 biopsies obtained from dogs with histologically-confirmed, surgically-removed MCT, treated with chemotherapy, and dead for MCT-related causes, was characterized by using Agilent Canine V2 4x44k DNA microarray, and compared with 40 samples obtained from dogs with histologically-confirmed, surgically-removed MCT that were alive after ~2 years of follow-up. Among the differentially expressed genes, 11 transcripts were chosen to validate DNA microarray results by qPCR and, then, their mRNA levels were measured in a cohort of 22 independent MCTs. Results: Statistical analysis identified a total of 377 differentially expressed genes (FDR 5%). The functional annotation analysis provided evidence of drug metabolism, steroid metabolism and cell cycle pathways; particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as targets. The Principal Component Analysis of the 22 cohort MCTs identified two separate clusters, and one of these referred to 4 dogs that had died due to MCT. Conclusions: SLCs and UGTs have been recently recognized in human cancer as important key factors in tumor progression and chemo-resistance. An in-depth analysis of their role in aggressive MCT might be useful in perspectives. Supporting grants: RC IZSVE 04/10