Abstract

Canine acanthomatous ameloblastomas (CAA), analogs of human ameloblastoma, are oral tumors of odontogenic origin for which the genetic drivers have remained undefined. By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation. Our findings newly identify a large-animal spontaneous cancer model to study the progression and treatment of RAS-driven cancer. More broadly, our study highlights the translational potential of canine cancer genome sequencing to benefit both humans and their companion animals.

Details

Title
Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer
Author
Saffari, Persiana S 1 ; Vapniarsky Natalia 2 ; Pollack, Anna S 1 ; Gong Xue 1 ; Vennam Sujay 1 ; Pollack, Andrew J 1 ; Verstraete Frank J M 3 ; West, Robert B 1 ; Arzi Boaz 3 ; Pollack, Jonathan R 1 

 Stanford University School of Medicine, Department of Pathology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
 UC Davis School of Veterinary Medicine, Department of Pathology, Microbiology & Immunology, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
 UC Davis School of Veterinary Medicine, Department of Surgical & Radiological Sciences, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
Publication year
2019
Publication date
Feb 2019
Publisher
Nature Publishing Group
e-ISSN
21579024
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2178602540
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.