Department of Clinical Sciences, Clinical Programs Center, College of Veterinary Medicine, Cornell University, Box 31, Ithaca, NY, 14853, USA.
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Sci Rep. 2021 Sep 7;11(1):17792. doi: 10.1038/s41598-021-97430-0.
Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.
成釉细胞瘤是一种牙源性肿瘤，在人类中罕见，但在狗中相对常见。由于犬的棘皮瘤性成釉细胞瘤（CAA）在临床病理和分子特征上与人类成釉细胞瘤（AM）具有共性，自发性 CAA 可以作为疾病的有用转化模型。然而，CAA 的分子基础及其与 AM 的比较尚不完全清楚。在这项研究中，我们使用 bulk RNA-seq 方法比较了 CAA 与 AM 的全基因组表达谱，并评估了其牙齿起源。为此，我们选择了健康的牙龈和犬口腔鳞状细胞癌作为对照。我们发现，异常的 RAS 信号和上皮-间充质转化细胞程序的激活参与了 CAA 的发病机制，并且 CAA 富含已知在 AM 中上调的基因，包括在牙齿发育早期表达的基因，这表明其具有高度的分子同源性。这些结果支持这样的模型，即具有自发性 CAA 的家犬具有针对 AM 的靶向治疗模式的临床前评估潜力。
