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Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer

2019; Springer Nature; Volume: 8; Issue: 2 Linguagem: Inglês

10.1038/s41389-019-0119-1

2157-9024

Persiana S. Saffari, Natalia Vapniarsky, Anna S. Pollack, Xue Gong, Sujay Vennam, Andrew J. Pollack, Frank J. Μ. Verstraete, Robert B. West, Boaz Arzi, Jonathan R. Pollack,

Hedgehog Signaling Pathway Studies

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.