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bioRxiv · 10.1101/2022.11.17.516327

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Estabrooks, T.·Gurinovich, A.·Pietruska, J.·Lewis, B.·Harvey, G.·Post, G.·Lambert, L.·Rodrigues, L. C.·White, M. E.·Lopes, C.·London, C. A.·Megquier, K.
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Abstract

BackgroundCanine 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. ObjectivesTo determine the relationships between genomic and clinical features including treatment and outcome in canine splenic HSA. Animals109 dogs with primary splenic HSA treated by splenectomy that had tumor sequencing via the FidoCure(R) Precision Medicine Platform targeted sequencing panel. MethodsPatient 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. ResultsSomatic 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 importanceDOX 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.

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Estabrooks, T., Gurinovich, A., Pietruska, J., Lewis, B., Harvey, G., Post, G., Lambert, L., Rodrigues, L. C., White, M. E., Lopes, C., London, C. A., Megquier, K.. 2022-11-17. Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma. https://doi.org/10.1101/2022.11.17.516327

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