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 | |
| State | Published - Feb 1 2019 |
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ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer
AU - Saffari, Persiana S.
AU - Vapniarsky Arzi, Natalia
AU - Pollack, Anna S.
AU - Gong, Xue
AU - Vennam, Sujay
AU - Pollack, Andrew J.
AU - Verstraete, Frank J
AU - West, Robert B.
AU - Arzi, Boaz
AU - Pollack, Jonathan R.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85061386482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061386482&partnerID=8YFLogxK
U2 - 10.1038/s41389-019-0119-1
DO - 10.1038/s41389-019-0119-1
M3 - Article
AN - SCOPUS:85061386482
VL - 8
JO - Oncogenesis
JF - Oncogenesis
SN - 2157-9024
IS - 2
M1 - 11
ER -