Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations

Detalhes bibliográficos
Autor(a) principal: Leal, Letícia Ferro
Data de Publicação: 2019
Outros Autores: Paula, Flávia Escremim de, De Marchi, Pedro, Viana, Luciano de Souza, Pinto, Gustavo Dix Junqueira, Carlos, Carolina Dias, Berardinelli, Gustavo Noriz, Miziara, José Elias, Silva, Carlos Maciel da, Silva, Eduardo Caetano Albino, Pereira, Rui, Oliveira, Marco Antonio de, Scapulatempo-Neto, Cristovam, Reis, R. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/62502
Resumo: Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR-exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.
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spelling Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutationsScience & TechnologyLung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR-exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.This work was supported by the Barretos Cancer Hospital; FINEP (MCTI/FINEP/MS/SCTIE/DECIT-CT-INFRA grant number 02/2010); Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer); and National Council for Scientifc and Technological Development (CNPq, Brazil).Nature ResearchUniversidade do MinhoLeal, Letícia FerroPaula, Flávia Escremim deDe Marchi, PedroViana, Luciano de SouzaPinto, Gustavo Dix JunqueiraCarlos, Carolina DiasBerardinelli, Gustavo NorizMiziara, José EliasSilva, Carlos Maciel daSilva, Eduardo Caetano AlbinoPereira, RuiOliveira, Marco Antonio deScapulatempo-Neto, CristovamReis, R. M.2019-032019-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/62502eng2045-23222045-232210.1038/s41598-019-39965-x30824880info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:31:45Zoai:repositorium.sdum.uminho.pt:1822/62502Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:27:01.550928Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
title Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
spellingShingle Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
Leal, Letícia Ferro
Science & Technology
title_short Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
title_full Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
title_fullStr Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
title_full_unstemmed Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
title_sort Mutational profle of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations
author Leal, Letícia Ferro
author_facet Leal, Letícia Ferro
Paula, Flávia Escremim de
De Marchi, Pedro
Viana, Luciano de Souza
Pinto, Gustavo Dix Junqueira
Carlos, Carolina Dias
Berardinelli, Gustavo Noriz
Miziara, José Elias
Silva, Carlos Maciel da
Silva, Eduardo Caetano Albino
Pereira, Rui
Oliveira, Marco Antonio de
Scapulatempo-Neto, Cristovam
Reis, R. M.
author_role author
author2 Paula, Flávia Escremim de
De Marchi, Pedro
Viana, Luciano de Souza
Pinto, Gustavo Dix Junqueira
Carlos, Carolina Dias
Berardinelli, Gustavo Noriz
Miziara, José Elias
Silva, Carlos Maciel da
Silva, Eduardo Caetano Albino
Pereira, Rui
Oliveira, Marco Antonio de
Scapulatempo-Neto, Cristovam
Reis, R. M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Leal, Letícia Ferro
Paula, Flávia Escremim de
De Marchi, Pedro
Viana, Luciano de Souza
Pinto, Gustavo Dix Junqueira
Carlos, Carolina Dias
Berardinelli, Gustavo Noriz
Miziara, José Elias
Silva, Carlos Maciel da
Silva, Eduardo Caetano Albino
Pereira, Rui
Oliveira, Marco Antonio de
Scapulatempo-Neto, Cristovam
Reis, R. M.
dc.subject.por.fl_str_mv Science & Technology
topic Science & Technology
description Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients' genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR-exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
2019-03-01T00:00:00Z
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2045-2322
10.1038/s41598-019-39965-x
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dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
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