Catalog of the 52 canids genomes.

Identifying genetic mutations contributing to solid tumors by altering the biological pathways related to tumor formation and development is essential for the development of targeted therapies. This study aimed to identify commonly mutated genes and altered pathways in canine solid tumors. Four dogs with different types of naturally occurring neoplasias (urothelial carcinoma, adenocarcinoma, rhabdomyosarcoma, and chondrosarcoma) were randomly selected and classified into carcinoma and sarcoma groups based on histopathological findings. Tumor tissues were analyzed using whole-genome sequencing, and significant variants shared within each tumor group were identified. Gene set enrichment analyses were conducted to compare the biological and functional pathways altered by the mutations in each carcinoma and sarcoma group. Forty-three and fifty-eight genes were identified in the carcinoma and sarcoma groups, respectively. Distinctions between the two tumor groups were noted for mutations related to tumor metastatic function. Mutations were identified in genes encoding cell adhesion molecules in the carcinoma group, whereas significant variations in extracellular matrix-related molecules were evident in the sarcoma group. This study revealed mutations and modified pathways associated with immune and tumor metastatic functions in canine carcinoma and sarcoma, indicating their significant relevance to the development and progression of each tumor group. Additionally, the distinctions indicated that different therapeutic approaches were required for each tumor group.通过改变与肿瘤发生发展相关的生物学通路来识别促成实体瘤的基因突变，对于靶向治疗的研发至关重要。本研究旨在识别犬类实体瘤中常见的突变基因与异常调控通路。本研究随机选取4只患有不同类型自发性肿瘤的犬只，其肿瘤类型分别为尿路上皮癌（urothelial carcinoma）、腺癌（adenocarcinoma）、横纹肌肉瘤（rhabdomyosarcoma）与软骨肉瘤（chondrosarcoma），并根据组织病理学结果将其分为癌组与肉瘤组。对肿瘤组织开展全基因组测序（whole-genome sequencing）分析，进而识别出每个肿瘤组内共有的显著变异。通过基因集富集分析（gene set enrichment analysis）对比癌组与肉瘤组中突变所调控的生物学与功能通路差异。癌组与肉瘤组分别鉴定出43个与58个突变基因。两组肿瘤在与肿瘤转移功能相关的突变特征上存在显著差异：癌组中检出编码细胞黏附分子（cell adhesion molecules）的基因突变，而肉瘤组则表现出细胞外基质（extracellular matrix）相关分子的显著变异。本研究揭示了犬类癌与肉瘤中与免疫及肿瘤转移功能相关的突变与通路异常，表明这些变异与两类肿瘤的发生发展密切相关。此外，两组间的差异提示，针对这两类肿瘤需采用差异化的治疗策略。