Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer
Aguado, Cristina (Quirón Dexeus University Hospital)
Teixidó, Cristina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Román, Ruth (Quirón Dexeus University Hospital)
Reyes, Roxana (Hospital Clínic i Provincial de Barcelona)
Giménez-Capitán, Ana (Quirón Dexeus University Hospital)
Marin, Elba (Hospital Clínic i Provincial de Barcelona)
Cabrera, Carlos (Grup Quirónsalud (Barcelona, Catalunya))
Viñolas, Nuria (Hospital Clínic i Provincial de Barcelona)
Castillo, Sergi (Hospital General de Granollers)
Muñoz, Silvia (Hospital General de Granollers)
Arcocha, Ainara (Hospital Clínic i Provincial de Barcelona)
López Vilaró, Laura (Institut d'Investigació Biomèdica Sant Pau)
Sullivan, Ivana (Institut d'Investigació Biomèdica Sant Pau)
Aldeguer, Erika (Quirón Dexeus University Hospital)
Rodríguez, Sonia (Quirón Dexeus University Hospital)
Moya, Irene (Grup Quirónsalud (Barcelona, Catalunya))
Viteri, Santiago (Quiron Salud Group)
Cardona Zorrilla, Andrés Felipe (Clínica del Country)
Palmero, Ramon (L'Hospitalet)
Sainz, Cristina (Centro de Investigación Biomédica en Red de Cáncer)
Mesa-Guzmán, Miguel (Universidad Pública de Navarra)
Lozano, Maria D. (Universidad Pública de Navarra)
Aguilar-Hernández, Andrés (Grup Quirónsalud (Barcelona, Catalunya))
Martínez-Bueno, Alejandro (Grup Quirónsalud (Barcelona, Catalunya))
González-Cao, María (Grup Quirónsalud (Barcelona, Catalunya))
Gonzalvo, Elena (Hospital Clínic i Provincial de Barcelona)
Leenders, William P. J. (Radboud Institute for Molecular Life Sciences)
Rosell, Rafael (Universitat Autònoma de Barcelona. Departament de Medicina)
Montuenga, Luis M. (Universidad Pública de Navarra)
Prat, Aleix (Hospital Clínic i Provincial de Barcelona)
Molina-Vila, Miguel Ángel (Quirón Dexeus University Hospital)
Reguart, Noemi (Hospital Clínic i Provincial de Barcelona)

Date:	2020
Abstract:	We studied MET alterations in 474 advanced non-small-cell lung cancer (NSCLC) patients by nCounter, an RNA-based technique. We identified 3% with MET Δex14 mRNA and 3. 5% with very-high MET mRNA expression, a surrogate of MET amplification. MET alterations identified by nCounter correlated with clinical benefit from MET inhibitors. Quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies. 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 MET Δex14 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 MET Δex14, 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.
Grants:	Instituto de Salud Carlos III FIS-PI19-00098 Instituto de Salud Carlos III FIS-PI16-00890
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amplification ; Expression ; Lung cancer ; MET ; RNA ; Skipping
Published in:	Molecular Oncology, Vol. 15 (december 2020) , p. 350-363, ISSN 1878-0261

DOI: 10.1002/1878-0261.12861
PMID: 33236532

14 p, 2.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles