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

  • Author(s): Saffari, PS
  • Vapniarsky, N
  • Pollack, AS
  • Gong, X
  • Vennam, S
  • Pollack, AJ
  • Verstraete, FJM
  • West, RB
  • Arzi, B
  • Pollack, JR
  • et al.
Abstract

© 2019, The Author(s). 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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