Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Background: Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells associated with short survival times. Understanding the genomic landscape of HSA is critical to developing more effective therapeutic strategies. Objectives: To determine the relationships between genomic and clinical features including treatment and outcome in canine splenic HSA. Animals: 109 dogs with primary splenic HSA treated by splenectomy that had tumor sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel. Methods: Patient signalment, weight, metastasis at diagnosis, treatment, and survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables and outcome were assessed. Results: Somatic mutations in TP53 (n = 45), NRAS (n = 20), and PIK3CA (n = 19) were most common. Survival was associated with metastases at diagnosis, germline variants in SETD2 and NOTCH1, and nominally with breed. Age at diagnosis was associated with NRAS mutations and breed. TP53 and PIK3CA mutations were found in larger dogs, germline SETD2 variants in smaller dogs. Doxorubicin (DOX) treatment did not significantly improve survival time, while targeted therapies had a significant early survival benefit. Conclusions and clinical importance: DOX treatment may provide limited clinical benefit for dogs with splenic HSA, while targeted therapy may provide early survival benefit. Genetic signatures associated with splenic HSA may be useful in guiding targeted therapy to improve outcomes. Germline variants, age, size, and breed may be useful prognostic factors and provide insight into the genomic landscape of the tumor. ### Competing Interest Statement CAL is a paid consultant for the One Health Company and a member of their Scientific Advisory; BL is a member of the One Health Company Board; KM has acted as an unpaid Special Advisor to the One Health Company; GH, GP, LL, LR, MEW, and CL are full-time employees of the One Health Company.