We have successfully developed a canine cancer gene panel that we have called the Canine Oncopanel, using cutting-edge, next-generation sequencing technology (NGS). The Canine Oncopanel allows sequencing of 283 cancer-related genes and detection of mutations within these genes that may drive the tumor cells to proliferate and survive. The canine oncopanel sequences a total target region that equates to ~3% of the canine genome. Analyzing the genomic composition of this broad target region allows evaluation of common genomic alterations that can lead to the development of cancer. The Canine Oncopanel is suitable to map mutation profiles and identify driver mechanisms in both common and rare canine cancers to provide a better understanding of the tumor genome and its biology.
Furthermore, as in human cancer genetics, targeted sequencing panels like the canine oncopanel are being used to provide an estimate of total mutational burden of the tumor, which has relevance in predicting response to certain immunotherapies. In addition, through identification of clinically-actionable biomarkers, the Canine Oncopanel serves as a genomic diagnostic tool that may guide selection of appropriate targeted therapies and possibly predict treatment response and patient outcome. To date, we have analyzed 60 canine DLBCL (cDLBCL) cases using the validated Canine Oncopanel. Putative driver genes were found in 51 cases, which included driver genes previously identified by whole exome sequencing and RNA sequencing in cDLBCL or human DLBCL (hDLBCL), as well as novel drivers found in other cancers. Clinical follow-up data were collected retrospectively and analyzed in the context of mutational profiles. Mutations in genes including TRAF3 and TP53 appeared to occur more frequently in cases with shorter overall survival times, suggesting that these mutations might delineate a more aggressive subgroup of cDLBCL and serve as prognostic markers. However, this hypothesis will need to be tested in a prospective clinical trial.