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Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: from the ETOP Lungscape Project

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Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: from the ETOP Lungscape Project

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dc.contributor.author Kerr, K. M. es_ES
dc.contributor.author Dafni, U. es_ES
dc.contributor.author Schulze, K. es_ES
dc.contributor.author Thunnissen, E. es_ES
dc.contributor.author Bubendorf, L. es_ES
dc.contributor.author Hager, H. es_ES
dc.contributor.author Finn, S. es_ES
dc.contributor.author Biernat, W. es_ES
dc.contributor.author Vliegen, L. es_ES
dc.contributor.author Losa, J. H. es_ES
dc.contributor.author Marchetti, A. es_ES
dc.contributor.author Cheney, R. es_ES
dc.contributor.author Warth, A. es_ES
dc.contributor.author Speel, E.-J. es_ES
dc.contributor.author Jantus-Lewintre, Eloisa es_ES
dc.date.accessioned 2018-10-25T04:33:16Z
dc.date.available 2018-10-25T04:33:16Z
dc.date.issued 2018 es_ES
dc.identifier.issn 0923-7534 es_ES
dc.identifier.uri http://hdl.handle.net/10251/111248
dc.description.abstract [EN] Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I¿III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is¿>1% for most of the ~150 (13 genes) mutations covered in the multiplex test. Results Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8¿years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63¿µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I¿III NSCLC cohort, none of the mutations characterized showed prognostic significance. es_ES
dc.language Inglés es_ES
dc.publisher Oxford University Press es_ES
dc.relation.ispartof Annals of Oncology es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Non-small-cell lung cancer es_ES
dc.subject Multiplex mutation analysis es_ES
dc.subject EGFR, KRAS, PIK3CA es_ES
dc.subject Prognosis molecular staging es_ES
dc.subject.classification MICROBIOLOGIA es_ES
dc.title Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: from the ETOP Lungscape Project es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1093/annonc/mdx629 es_ES
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia es_ES
dc.description.bibliographicCitation Kerr, KM.; Dafni, U.; Schulze, K.; Thunnissen, E.; Bubendorf, L.; Hager, H.; Finn, S.... (2018). Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: from the ETOP Lungscape Project. Annals of Oncology. 29(1):200-208. doi:10.1093/annonc/mdx629 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://dx.doi.org/10.1093/annonc/mdx629 es_ES
dc.description.upvformatpinicio 200 es_ES
dc.description.upvformatpfin 208 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 29 es_ES
dc.description.issue 1 es_ES
dc.relation.pasarela 352269 es_ES


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