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Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)

BACKGROUND: The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co‐occurring mutations of non‐small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). METHODS: This was a retrospective cross‐sectional study o...

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Autores principales: Mascarenhas, Eldsamira, Gelatti, Ana Caroline, Araújo, Luiz Henrique, Baldotto, Clarissa, Mathias, Clarissa, Zukin, Mauro, Werutsky, Gustavo, Pacheco, Patricia, Gomes, Rafaela, de Castro, Gilberto, Cordeiro de Lima, Vladmir Cláudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919136/
https://www.ncbi.nlm.nih.gov/pubmed/33314759
http://dx.doi.org/10.1111/1759-7714.13777
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author Mascarenhas, Eldsamira
Gelatti, Ana Caroline
Araújo, Luiz Henrique
Baldotto, Clarissa
Mathias, Clarissa
Zukin, Mauro
Werutsky, Gustavo
Pacheco, Patricia
Gomes, Rafaela
de Castro, Gilberto
Cordeiro de Lima, Vladmir Cláudio
author_facet Mascarenhas, Eldsamira
Gelatti, Ana Caroline
Araújo, Luiz Henrique
Baldotto, Clarissa
Mathias, Clarissa
Zukin, Mauro
Werutsky, Gustavo
Pacheco, Patricia
Gomes, Rafaela
de Castro, Gilberto
Cordeiro de Lima, Vladmir Cláudio
author_sort Mascarenhas, Eldsamira
collection PubMed
description BACKGROUND: The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co‐occurring mutations of non‐small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). METHODS: This was a retrospective cross‐sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma. RESULTS: We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P < 0.00001). Tumor mutational burden (TMB) analysis was available for 80.5% of samples tested, and 5.5% of samples had high TMB (≥ 20 mutations/Mb). In conclusion, this retrospective analysis of genomic data from NSCLC patients obtained by CGP showed that common abnormalities such as EGFR mutations and ALK rearrangements had similar frequency to those previously described by other groups using others strategies. Additionally, our data confirm an association between TP53 p.R337H, supposedly germline in nature, and somatic mutations in genes of the HER family. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling (CGP). The frequency of the most common driver mutations in this population was similar to that previously described in Brazil. WHAT THIS STUDY ADDS: TP53 was the most commonly comutated gene across samples. TP53 p.R337H was associated with somatic mutations in EGFR and ERBB2. Most samples had low TMB; only 5.5% of samples had high TMB.
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spelling pubmed-79191362021-03-05 Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418) Mascarenhas, Eldsamira Gelatti, Ana Caroline Araújo, Luiz Henrique Baldotto, Clarissa Mathias, Clarissa Zukin, Mauro Werutsky, Gustavo Pacheco, Patricia Gomes, Rafaela de Castro, Gilberto Cordeiro de Lima, Vladmir Cláudio Thorac Cancer Original Articles BACKGROUND: The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co‐occurring mutations of non‐small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). METHODS: This was a retrospective cross‐sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma. RESULTS: We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P < 0.00001). Tumor mutational burden (TMB) analysis was available for 80.5% of samples tested, and 5.5% of samples had high TMB (≥ 20 mutations/Mb). In conclusion, this retrospective analysis of genomic data from NSCLC patients obtained by CGP showed that common abnormalities such as EGFR mutations and ALK rearrangements had similar frequency to those previously described by other groups using others strategies. Additionally, our data confirm an association between TP53 p.R337H, supposedly germline in nature, and somatic mutations in genes of the HER family. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling (CGP). The frequency of the most common driver mutations in this population was similar to that previously described in Brazil. WHAT THIS STUDY ADDS: TP53 was the most commonly comutated gene across samples. TP53 p.R337H was associated with somatic mutations in EGFR and ERBB2. Most samples had low TMB; only 5.5% of samples had high TMB. John Wiley & Sons Australia, Ltd 2020-12-13 2021-03 /pmc/articles/PMC7919136/ /pubmed/33314759 http://dx.doi.org/10.1111/1759-7714.13777 Text en © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Mascarenhas, Eldsamira
Gelatti, Ana Caroline
Araújo, Luiz Henrique
Baldotto, Clarissa
Mathias, Clarissa
Zukin, Mauro
Werutsky, Gustavo
Pacheco, Patricia
Gomes, Rafaela
de Castro, Gilberto
Cordeiro de Lima, Vladmir Cláudio
Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title_full Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title_fullStr Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title_full_unstemmed Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title_short Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)
title_sort comprehensive genomic profiling of brazilian non‐small cell lung cancer patients (gbot 0118/lacog0418)
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919136/
https://www.ncbi.nlm.nih.gov/pubmed/33314759
http://dx.doi.org/10.1111/1759-7714.13777
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