Gain of FGF4 is a frequent event in KIT/PDGFRA/SDH/RAS-P WT GIST.
Genes Chromosomes Cancer
; 58(9): 636-642, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30887595
ABSTRACT
Gastrointestinal stromal tumors (GIST) lacking mutations in KIT/PDGFRA or RAS pathways and retaining an intact SDH complex are usually referred to as KIT/PDGFRA/SDH/RAS-P WT GIST or more simply quadruple WT GIST (~5% of all GIST). Despite efforts made, no recurrent genetic event in quadruple WT GIST has been identified so far. To further investigate this disease, we performed high throughput copy number analysis on quadruple WT GIST specimens identifying a recurrent focal gain in band 11q13.3 (involving FGF3/FGF4) in 6/8 cases. This event was not found in the other molecular GIST subgroups. FGF3/FGF4 duplication was associated with high expression of FGF4, both at mRNA and protein level, a growth factor normally not expressed in adult tissues or in KIT/PDGFRA-mutated GIST. FGFR1 was found to be the predominant FGF receptor expressed and phosphorylation of AKT was detected, suggesting that a FGF4-FGFR1 autocrine loop could stimulate downstream signaling in quadruple WT GIST. Together with the recent reports of quadruple WT cases carrying FGFR1 activating alterations, these findings strengthen the hypothesis of a potential involvement of FGFR pathway deregulation in quadruple WT GIST, which may represent a rationale for novel therapeutic approaches.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Duplicação Gênica
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Tumores do Estroma Gastrointestinal
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Fator 4 de Crescimento de Fibroblastos
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Neoplasias Gastrointestinais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Genes Chromosomes Cancer
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália