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

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

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article number11
JournalOncogenesis
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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