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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

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Ameloblastoma
Canidae
Animal Models
Mutation
Neoplasms
Ameloblasts
Odontogenic Tumors
Exome
Pets
Phosphotransferases
Cell Proliferation
Genome
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer. / Saffari, Persiana S.; Vapniarsky Arzi, Natalia; Pollack, Anna S.; Gong, Xue; Vennam, Sujay; Pollack, Andrew J.; Verstraete, Frank J; West, Robert B.; Arzi, Boaz; Pollack, Jonathan R.

In: Oncogenesis, Vol. 8, No. 2, 11, 01.02.2019.

Research output: Contribution to journalArticle

Saffari, Persiana S. ; Vapniarsky Arzi, Natalia ; Pollack, Anna S. ; Gong, Xue ; Vennam, Sujay ; Pollack, Andrew J. ; Verstraete, Frank J ; West, Robert B. ; Arzi, Boaz ; Pollack, Jonathan R. / Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer. In: Oncogenesis. 2019 ; Vol. 8, No. 2.
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