Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas.
Genes (Basel)
; 10(7)2019 07 04.
Article
em En
| MEDLINE
| ID: mdl-31277422
ABSTRACT
While the genetic contributions to the predisposition of Bernese mountain dogs (BMDs) to histiocytic sarcoma (HS) remains unclear, some insights into key genetic drivers have been gained. Our group recently reported a mutation in the PTPN11 gene (E76K). We have now identified a second missense mutation in PTPN11 (G503V), and a mutation in KRAS (Q61H) present in HS cell lines. These mutations are associated with malignancies in humans, and known to be gain-of-function mutations that result in activation of the mitogen-activated protein kinase (MAPK) pathway. The goal of the present study was to evaluate the prevalence of these mutations in a large sample of HS cases from BMDs and golden retrievers, and in lymphoma cases, from a cohort of BMDs. Mutations in PTPN11 were present in HS in 41/96 (43%) BMDs, and in 3/13 (23%) golden retrievers. PTPN11 mutations E76K and G503V did not coexist in the same neoplasm. The KRAS mutation was much less frequent, with a prevalence of 3.1% (3/96). We did not identify either PTPN11 nor KRAS mutations in any of the lymphoma samples. These results point out the potential relevance of PTPN11 and KRAS mutations as activators of the oncogenic MAPK pathway for canine HS, particularly in BMDs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Doenças do Cão
/
Cães
/
Sarcoma Histiocítico
/
Proteína Tirosina Fosfatase não Receptora Tipo 11
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos