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

doi:10.1038/s41389-019-0119-1

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

School of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

9 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 language	English (US)
Article number	11
Journal	Oncogenesis
Volume	8
Issue number	2
DOIs	https://doi.org/10.1038/s41389-019-0119-1
State	Published - Feb 1 2019

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

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

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Vennam, Sujay

AU - Pollack, Andrew J.

AU - Verstraete, Frank J.M.

AU - West, Robert B.

AU - Arzi, Boaz

AU - Pollack, Jonathan R.

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

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