Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States of America.
McDonnell Genome Institute, Washington University, St. Louis, MO, United States of America.
PLoS One. 2021 Feb 8;16(2):e0246443. doi: 10.1371/journal.pone.0246443. eCollection 2021.
Osteosarcoma is a rare disease in children but is one of the most common cancers in adult large breed dogs. The mutational landscape of both the primary and pulmonary metastatic tumor in two dogs with appendicular osteosarcoma (OSA) was comprehensively evaluated using an automated whole genome sequencing, exome and RNA-seq pipeline that was adapted for this study for use in dogs. Chromosomal lesions were the most common type of mutation. The mutational landscape varied substantially between dogs but the lesions within the same patient were similar. Copy number neutral loss of heterozygosity in mutant TP53 was the most significant driver mutation and involved a large region in the middle of chromosome 5. Canine and human OSA is characterized by loss of cell cycle checkpoint integrity and DNA damage response pathways. Mutational profiling of individual patients with canine OSA would be recommended prior to targeted therapy, given the heterogeneity seen in our study and previous studies.
骨肉瘤在儿童中较为罕见，但在成年大型犬中却是最常见的癌症之一。本研究采用一种自动化全基因组测序、外显子组和 RNA-seq 分析流程，对两只患有附肢骨肉瘤（OSA）的犬的原发性和肺转移肿瘤进行了全面评估。结果显示，染色体病变是最常见的突变类型。尽管不同犬种的突变景观存在显著差异，但同一患者的病变却较为相似。在突变型 TP53 中，杂合性缺失是最重要的驱动突变，涉及染色体 5 中部的一个大片段。犬类和人类的骨肉瘤的特点是细胞周期检查点完整性和 DNA 损伤反应途径的丧失。鉴于本研究和以往研究中观察到的异质性，建议在对犬类 OSA 患者进行靶向治疗之前，对其进行突变分析。
