犬血管内皮细胞肉瘤（HSA）是一种侵袭性癌症，生存期较短。了解HSA的基因组景观可能有助于开发狗类的治疗策略，同时也可能为罕见而侵袭性的人类肉瘤血管肉瘤提供治疗方法。本研究的目标是建立一个利用真实世界基因组和临床数据的框架，为兽医肿瘤精准医学奠定基础，以及确定犬脾HSA的基因组和临床特征之间的关系。收集了通过FidoCure®精准医学平台目标测序面板进行肿瘤测序的109只脾脏原发肿瘤HSA患犬，经脾脏切除术治疗。回顾性评估了患者的信号特点、体重、诊断时是否存在转移以及总生存时间。评估了各个基因的基因组变异发生率及其与患者结局等变量的关系。TP53（n=44）、NRAS（n=20）和PIK3CA（n=19）的体细胞突变最常见。生存与诊断时转移的存在以及SETD2和NOTCH1的生殖系等位变异有关。诊断时的年龄与NRAS的体细胞突变和品种有关。大型犬中发现了TP53和PIK3CA的体细胞突变，而小型犬中发现了SETD2的生殖系变异。我们发现了与临床变量（包括年龄、品种和总生存时间）相关的体细胞突变和生殖系变异。这些基因变化可能是有用的预后因素，并揭示了血管肉瘤的基因组景观。© 2023年作者。由约翰·威利和儿子有限公司出版的兽医与比较肿瘤学。

Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.