Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer. Oncogenesis Saffari, P. S., Vapniarsky, N., Pollack, A. S., Gong, X., Vennam, S., Pollack, A. J., Verstraete, F. J., West, R. B., Arzi, B., Pollack, J. R. 2019; 8 (2): 11


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.

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