Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer
Clin. transl. oncol. (Print)
; 20(7): 881-888, jul. 2018. ilus, tab, graf
Artigo
em Inglês
| IBECS
| ID: ibc-173639
Biblioteca responsável:
ES1.1
Localização: BNCS
ABSTRACT
Purpose:
Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. Methods and patients 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations. METex14 mutations, MET copy number alterations and the levels of MET protein were determined by Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry, respectively. Concurrent alterations of other important cancer genes and immunostaining of the downstream effector, phopho-S6, were also determined.Results:
METex14 mutations and MET amplification were detected in seven tumors. MET genetic alterations were found predominantly in the lung adenocarcinoma (ADC) and PSC histopathologies. High levels of MET protein were found in most MET-amplified tumors, but not in all METex14-mutated tumors. Strong phopho-S6 staining was observed in about half of the MET-activated tumors. One tumor with METex14 exhibited concurrent ERBB2 amplification.Conclusions:
MET activation, by either METex14 mutations or amplification, is characteristic of a subset of early stage NSCLCs and may coexist with ERBB2 amplification. This may have potential therapeutic implications. The presence of METex14 mutations was associated with low levels of MET protein, which may limit the use of total MET immunostaining as a marker for preselecting patients for MET-targeted therapiesRESUMEN
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Coleções:
Bases de dados nacionais
/
Espanha
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
Problema de saúde:
Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis
Base de dados:
IBECS
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Proteínas Proto-Oncogênicas c-met
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Neoplasias Pulmonares
Tipo de estudo:
Estudo diagnóstico
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Estudo prognóstico
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Estudo de rastreamento
Limite:
Adulto
/
Idoso
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Feminino
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Humanos
/
Masculino
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2018
Tipo de documento:
Artigo
Instituição/País de afiliação:
Bellvitge Biomedical Research Institute (IDIBELL)/Spain
/
Université Grenoble Alpes/France