Research Grants Program Office (RGPO)
Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer.
- Author(s): Saffari, Persiana S
- Vapniarsky, Natalia
- Pollack, Anna S
- Gong, Xue
- Vennam, Sujay
- Pollack, Andrew J
- Verstraete, Frank JM
- West, Robert B
- Arzi, Boaz
- Pollack, Jonathan R
- et al.
Published Web Locationhttps://doi.org/10.1038/s41389-019-0119-1
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.