Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer
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 nCou...
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Format: | Article |
Language: | English |
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Wiley
2021-02-01
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Series: | Molecular Oncology |
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Online Access: | https://doi.org/10.1002/1878-0261.12861 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cristina Aguado Cristina Teixido Ruth Román Roxana Reyes Ana Giménez‐Capitán Elba Marin Carlos Cabrera Nuria Viñolas Sergi Castillo Silvia Muñoz Ainara Arcocha Laura López‐Vilaró Ivana Sullivan Erika Aldeguer Sonia Rodríguez Irene Moya Santiago Viteri Andrés Felipe Cardona Ramon Palmero Cristina Sainz Miguel Mesa‐Guzmán Maria D. Lozano Andrés Aguilar‐Hernández Alejandro Martínez‐Bueno María González‐Cao Elena Gonzalvo William P. J. Leenders Rafael Rosell Luis M. Montuenga Aleix Prat Miguel A. Molina‐Vila Noemi Reguart |
spellingShingle |
Cristina Aguado Cristina Teixido Ruth Román Roxana Reyes Ana Giménez‐Capitán Elba Marin Carlos Cabrera Nuria Viñolas Sergi Castillo Silvia Muñoz Ainara Arcocha Laura López‐Vilaró Ivana Sullivan Erika Aldeguer Sonia Rodríguez Irene Moya Santiago Viteri Andrés Felipe Cardona Ramon Palmero Cristina Sainz Miguel Mesa‐Guzmán Maria D. Lozano Andrés Aguilar‐Hernández Alejandro Martínez‐Bueno María González‐Cao Elena Gonzalvo William P. J. Leenders Rafael Rosell Luis M. Montuenga Aleix Prat Miguel A. Molina‐Vila Noemi Reguart Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer Molecular Oncology amplification expression lung cancer MET RNA skipping |
author_facet |
Cristina Aguado Cristina Teixido Ruth Román Roxana Reyes Ana Giménez‐Capitán Elba Marin Carlos Cabrera Nuria Viñolas Sergi Castillo Silvia Muñoz Ainara Arcocha Laura López‐Vilaró Ivana Sullivan Erika Aldeguer Sonia Rodríguez Irene Moya Santiago Viteri Andrés Felipe Cardona Ramon Palmero Cristina Sainz Miguel Mesa‐Guzmán Maria D. Lozano Andrés Aguilar‐Hernández Alejandro Martínez‐Bueno María González‐Cao Elena Gonzalvo William P. J. Leenders Rafael Rosell Luis M. Montuenga Aleix Prat Miguel A. Molina‐Vila Noemi Reguart |
author_sort |
Cristina Aguado |
title |
Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer |
title_short |
Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer |
title_full |
Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer |
title_fullStr |
Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer |
title_full_unstemmed |
Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancer |
title_sort |
multiplex rna‐based detection of clinically relevant met alterations in advanced non‐small cell lung cancer |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2021-02-01 |
description |
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. |
topic |
amplification expression lung cancer MET RNA skipping |
url |
https://doi.org/10.1002/1878-0261.12861 |
work_keys_str_mv |
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doaj-5db041644f0248ee90bd178c373b18672021-02-04T03:25:42ZengWileyMolecular Oncology1574-78911878-02612021-02-0115235036310.1002/1878-0261.12861Multiplex RNA‐based detection of clinically relevant MET alterations in advanced non‐small cell lung cancerCristina Aguado0Cristina Teixido1Ruth Román2Roxana Reyes3Ana Giménez‐Capitán4Elba Marin5Carlos Cabrera6Nuria Viñolas7Sergi Castillo8Silvia Muñoz9Ainara Arcocha10Laura López‐Vilaró11Ivana Sullivan12Erika Aldeguer13Sonia Rodríguez14Irene Moya15Santiago Viteri16Andrés Felipe Cardona17Ramon Palmero18Cristina Sainz19Miguel Mesa‐Guzmán20Maria D. Lozano21Andrés Aguilar‐Hernández22Alejandro Martínez‐Bueno23María González‐Cao24Elena Gonzalvo25William P. J. Leenders26Rafael Rosell27Luis M. Montuenga28Aleix Prat29Miguel A. Molina‐Vila30Noemi Reguart31Laboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainThoracic Oncology Unit Department of Pathology Hospital Clínic Barcelona SpainLaboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainThoracic Oncology Unit Department of Medical Oncology Hospital Clínic Barcelona SpainLaboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainTranslational Genomics and Targeted Therapeutics in Solid Tumors Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainThoracic Oncology Unit Department of Medical Oncology Hospital Clínic Barcelona SpainDivision of Medical Oncology Hospital General de Granollers Barcelona SpainDivision of Medical Oncology Hospital General de Granollers Barcelona SpainThoracic Oncology Unit Department of Medical Oncology Hospital Clínic Barcelona SpainDepartment of Pathology Hospital de la Santa Creu i Sant Pau Barcelona SpainDivision of Medical Oncology Hospital de la Santa Creu i Sant Pau Barcelona SpainLaboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainLaboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainFoundation for Clinical and Applied Cancer Research‐FICMAC Bogotá ColombiaDivision of Medical Oncology Catalan Institute of Oncology L'Hospitalet Barcelona SpainCenter for Applied Medical Research (CIMA) University of Navarra SpainDepartment of Thoracic Surgery University of Navarra Pamplona SpainCIBERONC Madrid SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainThoracic Oncology Unit Department of Pathology Hospital Clínic Barcelona SpainDepartment of Biochemistry Radboud Institute for Molecular Life Sciences Nijmegen The NetherlandsDr Rosell Oncology Institute Dexeus University Hospital Quiron Salud Group Barcelona SpainCenter for Applied Medical Research (CIMA) University of Navarra SpainTranslational Genomics and Targeted Therapeutics in Solid Tumors Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona SpainLaboratory of Oncology, Pangaea Oncology Quirón Dexeus University Hospital Barcelona SpainTranslational Genomics and Targeted Therapeutics in Solid Tumors Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona SpainMET 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.https://doi.org/10.1002/1878-0261.12861amplificationexpressionlung cancerMETRNAskipping |