Interrogating the Clinical Implications of Somatic Mutations in Canine Splenic Hemangiosarcoma
Introduction
Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells typically associated with short survival times. Understanding the genomic landscape of canine HSA is critical to develop more effective therapeutic strategies. Recent studies indicate that several key mutations such as those involving PIK3CA are found in HSA.
The objective of this study was to leverage a highly curated large population of dogs with splenic HSA to determine whether specific somatic mutations are associated with metastasis at presentation and/or overall survival time.
Methods
Splenic HSA tumor samples from 99 dogs were analyzed using the Next-Generation Sequencing panel from the FidoCure® Precision Medicine Platform. Patient signalment, presence of metastasis at diagnosis, doxorubicin treatment, and overall survival time were evaluated. The incidence of specific mutations and their relationship to outcome were assessed.
Results
Metastasis at diagnosis was present in 29.2% of patients and negatively correlated with median survival time (136d vs. 260d, p=0.022). Interestingly, treatment with doxorubicin did not improve outcome in this population. TP53 mutation was common (40%) and was associated with shorter median survival time (147d vs. 311d, p=0.054). Mutations were also identified in PIK3CA (15%), NRAS (13%), and PTEN (5%) although no correlation with survival time was noted.
Conclusion
These data suggest that TP53 mutation is associated with a poor prognosis in dogs with splenic HSA and that the use of doxorubicin may not improve outcome.
Additional analysis of this patient cohort is ongoing, including the contribution of several other novel somatic mutations and their relationship to disease biology.