Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer.
Mol Oncol
; 15(2): 350-363, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33236532
ABSTRACT
MET inhibitors have shown activity in non-small-cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with METΔex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For METΔex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very-high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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RNA Neoplásico
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Regulação Neoplásica da Expressão Gênica
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Análise de Sequência de RNA
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Carcinoma Pulmonar de Células não Pequenas
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Proteínas Proto-Oncogênicas c-met
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Neoplasias Pulmonares
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article