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https://hdl.handle.net/1822/67600
Título: | Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs |
Autor(es): | Martinho, Olga Gouveia, António Pereira, Marta Sofia Carvalho Ribeiro Viana Silva, Paula Pimenta, Amadeu Reis, R. M. Lopes, José Manuel |
Palavras-chave: | Adult Aged Aged, 80 and over Biomarkers, Tumor Extracellular Signal-Regulated MAP Kinases Female Gastrointestinal Neoplasms Gastrointestinal Stromal Tumors Humans Male Middle Aged Mitogen-Activated Protein Kinase Kinases Mutations Prognosis Proto-Oncogene Proteins B-raf Proto-Oncogene Proteins c-kit Proto-Oncogene Proteins p21(ras) Receptor, Platelet-Derived Growth Factor alpha Retrospective Studies Signal Transduction Activation GISTs MAP kinase Wild-type |
Data: | Jul-2009 |
Editora: | Blackwell Publishing |
Revista: | Histopathology |
Resumo(s): | Aims: Gastrointestinal stromal tumours (GISTs) are commonly driven by oncogenic mutations in KIT and PDGFRA. However, 10-40% of these patients are wild-type for these genes. The prognostic significance of wild-type GISTs is controversial, and they rarely respond to imatinib. The aim of this study was to elucidate the molecular lesions underlying wild-type GISTs tumorigenesis. Methods and results: Twenty-nine KIT and PDGFRA wild-type GISTs were re-assessed for the presence of 'cryptic'KIT exon 11 duplications. Using a specific polymerase chain reaction assay, three previously undetected mutations were identified. In the remaining 26 wild-type GISTs, KIT, stem cell factor (SCF), phospho-KIT and phospho-ERK expression was evaluated by immunohistochemistry. Samples were screened for gain-of-function mutations in the mitogen-activated protein kinase (MAPK) cascade. KIT and SCF co-expression associated with KIT activation was observed in approximately 30% of cases. Furthermore, phospho-ERK expression showed that MAPK is activated in approximately 30% of cases. None of RAS family (H-, K- and N-RAS) oncogenes exhibited activating mutations, whereas BRAF mutations were found in approximately 4% of cases. Conclusions: In the absence of RAS mutations, MAPK could be activated through SCF/KIT autocrine/paracrine mechanisms and/or mutated BRAF in a subset of KIT/PDGFRA wild-type GISTs. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/67600 |
DOI: | 10.1111/j.1365-2559.2009.03323.x |
ISSN: | 0309-0167 |
e-ISSN: | 1365-2559 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito autor |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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martinho2009.pdf Acesso restrito! | 690,06 kB | Adobe PDF | Ver/Abrir |