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

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.

SUBMITTER: Saffari PS

PROVIDER: S-EPMC6370874 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Saffari Persiana S PS Vapniarsky Natalia N Pollack Anna S AS Gong Xue X Vennam Sujay S Pollack Andrew J AJ Verstraete Frank J M FJM West Robert B RB Arzi Boaz B Pollack Jonathan R JR

Oncogenesis 20190211 2

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 ...[more]

PMID: 30741938

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