GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi.
Br J Cancer
; 117(6): 884-887, 2017 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-28809862
ABSTRACT
BACKGROUND:
Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.METHODS:
We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.RESULTS:
For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.CONCLUSIONS:
Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Neoplasias da Coroide
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Subunidades alfa de Proteínas de Ligação ao GTP
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Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
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Proteínas Adaptadoras de Transdução de Sinal
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Mutação
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Proteínas de Neoplasias
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Nevo
Limite:
Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Holanda