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Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation

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dc.contributor.authorFernandes, Maria Gabriela O.
dc.contributor.authorJacob, Maria
dc.contributor.authorMartins, Natália
dc.contributor.authorMoura, Conceição Souto
dc.contributor.authorGuimarães, Susana
dc.contributor.authorPereira Reis, Joana
dc.contributor.authorJustino, Ana
dc.contributor.authorPina, Maria João
dc.contributor.authorCirnes, Luís
dc.contributor.authorSousa, Catarina
dc.contributor.authorPinto, Josué
dc.contributor.authorMarques, José Agostinho
dc.contributor.authorMachado, José Carlos
dc.contributor.authorHespanhol, Venceslau
dc.contributor.authorCosta, José Luis
dc.date.accessioned2019-11-19T17:29:18Z
dc.date.available2019-11-19T17:29:18Z
dc.date.issued2019
dc.description.abstractIdentification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. Methods: 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 (n = 22, 18.8%), ALK-mutated (n = 9, 7.7%), and unclassifiable (UC) (n = 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. Conclusions: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFernandes, M. G. O., Jacob, M., Martins, N., Moura, C. S., Guimarães, S., Reis, J. P., Justino, A., Pina, M. J., Cirnes, L., Sousa, C., Pinto, J., Marques, J. A., Machado, J. C., Hespanhol, V., & Costa, J. L. (2019). Targeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementation. Cancers, 11(9), Artigo 9. https://doi.org/10.3390/cancers11091229
dc.identifier.doi10.3390/cancers11091229
dc.identifier.urihttp://hdl.handle.net/10400.22/14843
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770536/pdf/cancers-11-01229.pdfpt_PT
dc.subjectLung cancerpt_PT
dc.subjectmolecular profilingpt_PT
dc.subjectnext-generation sequencingpt_PT
dc.subjectargeted therapypt_PT
dc.titleTargeted Gene Next-Generation Sequencing Panel in Patients with Advanced Lung Adenocarcinoma: Paving the Way for Clinical Implementationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue9pt_PT
oaire.citation.startPage1229pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume11pt_PT
person.familyNamePereira Reis
person.familyNameCirnes
person.givenNameJoana Catarina
person.givenNameLuís
person.identifier.ciencia-id5C1D-2276-334C
person.identifier.ciencia-idA412-0AC5-0780
person.identifier.orcid0000-0003-0823-4891
person.identifier.orcid0000-0002-2348-5878
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicatione2b84d13-9a83-45e7-b514-980ca9842fab
relation.isAuthorOfPublication17b01de2-29be-4571-8edd-d7fb6154b26c
relation.isAuthorOfPublication.latestForDiscoverye2b84d13-9a83-45e7-b514-980ca9842fab

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