Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation
Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. <i>Methods</i>: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Ge...
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Format: | Article |
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MDPI AG
2019-08-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/11/9/1229 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Gabriela O. Fernandes Maria Jacob Natália Martins Conceição Souto Moura Susana Guimarães Joana Pereira Reis Ana Justino Maria João Pina Luís Cirnes Catarina Sousa Josué Pinto José Agostinho Marques José Carlos Machado Venceslau Hespanhol José Luis Costa |
spellingShingle |
Maria Gabriela O. Fernandes Maria Jacob Natália Martins Conceição Souto Moura Susana Guimarães Joana Pereira Reis Ana Justino Maria João Pina Luís Cirnes Catarina Sousa Josué Pinto José Agostinho Marques José Carlos Machado Venceslau Hespanhol José Luis Costa Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation Cancers lung cancer targeted therapy next-generation sequencing molecular profiling |
author_facet |
Maria Gabriela O. Fernandes Maria Jacob Natália Martins Conceição Souto Moura Susana Guimarães Joana Pereira Reis Ana Justino Maria João Pina Luís Cirnes Catarina Sousa Josué Pinto José Agostinho Marques José Carlos Machado Venceslau Hespanhol José Luis Costa |
author_sort |
Maria Gabriela O. Fernandes |
title |
Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation |
title_short |
Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation |
title_full |
Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation |
title_fullStr |
Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation |
title_full_unstemmed |
Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation |
title_sort |
targeted gene next-generation sequencing panel in patients with advanced lung adenocarcinoma: paving the way for clinical implementation |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-08-01 |
description |
Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. <i>Methods</i>: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (<i>n</i> = 22, 18.8%), ALK-mutated (<i>n</i> = 9, 7.7%), and unclassifiable (UC) (<i>n</i> = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (κ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. <i>Conclusions</i>: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma. |
topic |
lung cancer targeted therapy next-generation sequencing molecular profiling |
url |
https://www.mdpi.com/2072-6694/11/9/1229 |
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doaj-ffde8d41d0514c6390b8218e2d57fde32020-11-24T21:22:57ZengMDPI AGCancers2072-66942019-08-01119122910.3390/cancers11091229cancers11091229Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical ImplementationMaria Gabriela O. Fernandes0Maria Jacob1Natália Martins2Conceição Souto Moura3Susana Guimarães4Joana Pereira Reis5Ana Justino6Maria João Pina7Luís Cirnes8Catarina Sousa9Josué Pinto10José Agostinho Marques11José Carlos Machado12Venceslau Hespanhol13José Luis Costa14Pulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPathology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalIdentification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. <i>Methods</i>: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (<i>n</i> = 22, 18.8%), ALK-mutated (<i>n</i> = 9, 7.7%), and unclassifiable (UC) (<i>n</i> = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (κ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. <i>Conclusions</i>: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.https://www.mdpi.com/2072-6694/11/9/1229lung cancertargeted therapynext-generation sequencingmolecular profiling |