Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Santiago Peralta,Andrew D Miller,Jennifer K Grenier,Kristiina Heikinheimo,Faraz Ahmed,Gerald E Duhamel,Angela L Mccleary-Wheeler,William P Katt

doi:10.1038/s41598-021-97430-0

Abstract

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.

Highlights

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs
Study material consisted of cryopreserved fresh tissue samples and archived formalinfixed paraffin-embedded (FFPE) tissues obtained from 37 client-owned dogs of variable age, breed, and sex, representing 20 canine acanthomatous ameloblastomas (CAA),[12] canine oral squamous cell carcinoma (COSCC), and 5 healthy gingiva (HGIN) samples (Table 1, Supplemental Table S1)
To further understand the molecular pathogenesis of CAA and characterize the extent of homology with AM, we explored the expression profile of CAA using a bulk RNA-seq approach and validated selected proteins by IHC

Summary

Introduction

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. 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.

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Conclusion