School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America.
Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States of America.
PLoS One. 2022 Sep 13;17(9):e0273705. doi: 10.1371/journal.pone.0273705. eCollection 2022.
Soft tissue sarcomas are pleiotropic tumors of mesenchymal cell origin. These tumors are rare in humans but common in veterinary practice, where they comprise up to 15% of canine skin and subcutaneous cancers. Because they present similar morphologies, primary sites, and growth characteristics, they are treated similarly, generally by surgical resection followed by radiation therapy. Previous studies have examined a variety of genetic changes as potential drivers of tumorigenesis and progression in soft tissue sarcomas as well as their use as markers for soft tissue sarcoma subtypes. However, few studies employing next generation sequencing approaches have been published. Here, we have examined gene expression patterns in canine soft tissue sarcomas using RNA-seq analysis of samples obtained from archived formalin-fixed and paraffin-embedded tumors. We provide a computational framework for using resulting data to categorize tumors, perform cross species comparisons and identify genetic changes associated with tumorigenesis. Functional overrepresentation analysis of differentially expressed genes further implicate both common and tumor-type specific transcription factors as potential mediators of tumorigenesis and aggression. Implications for tumor-type specific therapies are discussed. Our results illustrate the potential utility of this approach for the discovery of new therapeutic approaches to the management of canine soft tissue sarcomas and support the view that both common and tumor-type specific mechanisms drive the development of these tumors.
软组织肉瘤是间充质细胞来源的多能性肿瘤。这些肿瘤在人类中罕见，但在兽医实践中常见，在那里它们构成了高达 15%的犬皮肤和皮下癌症。由于它们具有相似的形态、原发部位和生长特征，因此它们的治疗方法相似，通常采用手术切除加放射治疗。先前的研究已经研究了多种遗传变化作为软组织肉瘤发生和进展的潜在驱动因素，以及它们作为软组织肉瘤亚型标志物的用途。然而，很少有使用下一代测序方法的研究发表。在这里，我们使用从存档的福尔马林固定和石蜡包埋肿瘤中获得的 RNA-seq 分析，检查了犬软组织肉瘤中的基因表达模式。我们提供了一个计算框架，用于使用这些数据对肿瘤进行分类、进行跨物种比较和识别与肿瘤发生相关的遗传变化。差异表达基因的功能过表达分析进一步暗示常见和肿瘤类型特异性转录因子可能是肿瘤发生和侵袭的潜在介质。讨论了对肿瘤类型特异性治疗的影响。我们的结果说明了这种方法在发现治疗犬软组织肉瘤的新方法方面的潜在应用，并支持这样一种观点，即常见和肿瘤类型特异性机制共同驱动这些肿瘤的发展。
