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Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients

Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform sho...

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Autores principales: Aran, Veronica, Zalis, Mariano, Montella, Tatiane, de Sousa, Carlos Augusto Moreira, Ferrari, Bruno L., Gil Ferreira, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539053/
https://www.ncbi.nlm.nih.gov/pubmed/34684076
http://dx.doi.org/10.3390/medicina57101039
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author Aran, Veronica
Zalis, Mariano
Montella, Tatiane
de Sousa, Carlos Augusto Moreira
Ferrari, Bruno L.
Gil Ferreira, Carlos
author_facet Aran, Veronica
Zalis, Mariano
Montella, Tatiane
de Sousa, Carlos Augusto Moreira
Ferrari, Bruno L.
Gil Ferreira, Carlos
author_sort Aran, Veronica
collection PubMed
description Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.
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spelling pubmed-85390532021-10-24 Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients Aran, Veronica Zalis, Mariano Montella, Tatiane de Sousa, Carlos Augusto Moreira Ferrari, Bruno L. Gil Ferreira, Carlos Medicina (Kaunas) Article Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted. MDPI 2021-09-29 /pmc/articles/PMC8539053/ /pubmed/34684076 http://dx.doi.org/10.3390/medicina57101039 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aran, Veronica
Zalis, Mariano
Montella, Tatiane
de Sousa, Carlos Augusto Moreira
Ferrari, Bruno L.
Gil Ferreira, Carlos
Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title_full Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title_fullStr Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title_full_unstemmed Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title_short Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients
title_sort evaluation of kras concomitant mutations in advanced lung adenocarcinoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539053/
https://www.ncbi.nlm.nih.gov/pubmed/34684076
http://dx.doi.org/10.3390/medicina57101039
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