Chief Scientific Officer and Founder Vidium Animal Health Scottsdale, Arizona, United States
Abstract:
Background: Growing evidence from dogs and humans supports the existence of abundant mutation-based biomarkers in canine cancers. Increasing use of clinical genomic diagnostics now provides another powerful data source for biomarker discovery.
Hypothesis/
Objectives: We analyzed clinical outcomes from cancer cases profiled with SearchLight DNA®, a canine cancer gene panel, to identify mutations with prognostic value.
Animals: One hundred twenty nine canine cancer cases analyzed with SearchLight DNA® and for which clinical outcome information was available were evaluated.
Methods: Clinical data points were collected through record review. Variables including mutated genes, individual mutations, signalment, and treatment were fitted with univariate and multivariate Cox proportional hazard models to identify factors associated with progression-free survival (PFS). The log-rank test compared PFS between patients receiving and not receiving targeted therapy prior to first progression or death.
Results: Combined genomic and outcomes analysis identified 243 mutations in 89 genes across 27 cancer types. Four genes (SMARCB1, FANCG, CDKN2B, MSH6) were significantly associated with shorter PFS in univariate analysis. Patients who received targeted therapy prior to first progression or death (n = 45) were associated with a significantly longer PFS (139 days) compared to those who did not (n = 84; PFS = 108 days; P = 0.0104).
Conclusions and clinical importance: We demonstrate the progression-free survival benefit of targeted therapy across multiple cancer types and identify novel mutations with prognostic value. This work highlights the potential for discovery of new actionable genomic information from clinical cases to benefit cancer management in dogs.
