Identification of Targetable Activating Mutations in Canine Acanthomatous Ameloblastoma

Dr. Santiago Peralta, DVM, Dipl. AVDC, FF-AVDC-OMFS, and his collaborators received a $10,000 grant from the Foundation for Veterinary Dentistry 

The project was immensely successful and led to important advances and discoveries regarding the molecular mechanisms involved with this common and locally destructive canine oral tumor. Importantly, they discovered that an acquired mutation in the HRAS gene (i.e. p.Q61R) is present in the vast majority of tumors. This discovery is of major veterinary and translational significance because it will serve as the basis for the development of novel precision-medicine based therapies in dogs in the near future. Moreover, such therapies will have the potential to replace or complement current surgical options, which are technically complex and expensive, and typically result in significant patient dysfunction. This discovery is also of comparative interest because it reveals molecular pathogenic similarities with the human counterpart of this tumor.

The tumor cell proliferation activity of this tumor was also studied as part of this project, and was compared to that of oral squamous cell carcinoma. Oral squamous cell carcinoma is also common in dogs, is very locally destructive and has metastatic potential. Despite significant differences in biologic behavior between canine acanthomatous ameloblastoma and squamous cell carcinoma (i.e. benign versus malignant), they are frequently confused and misdiagnosed due to overlapping clinical, radiographic and histological features. Their studies demonstrated that Ki67, which is a nuclear marker of cell proliferation that is easily localized with immunohistochemistry techniques, can be used to reliably distinguish between both tumor types. This is a significant contribution with immediate clinical, diagnostic and prognostic applications that will allow veterinarians and clients to make better informed surgical and medical decisions.

The discoveries associated with this project were published in two prominent scientific journals, and one of them was featured in the cover page:

1. Peralta S, McCleary-Wheeler AL, Duhamel GE, Heikinheimo K, Grenier JK. Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma. Vet Comp Oncol 2019; 17(3): 439-445,10.1111/vco.12487.
2. Peralta S, McCleary-Wheeler AL, Duhamel GE, Heikinheimo K, Grenier JK. Cover image, volume 17, issue 3. Vet Comp Oncol 2019; 17(3): i-i.
3. Peralta S, Grenier JK, McCleary-Wheeler AL, Duhamel GE. Ki67 labelling index of neoplastic epithelial cells differentiates canine acanthomatous ameloblastoma from oral squamous cell carcinoma. J Comp Pathol 2019; 171: 59-69.