Cargando…

Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma

Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generati...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Eun Young, Cho, Eun Na, Park, Heae Surng, Hong, Ji Young, Lim, Seri, Youn, Jong Pil, Hwang, Seung Yong, Chang, Yoon Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848002/
https://www.ncbi.nlm.nih.gov/pubmed/26785607
http://dx.doi.org/10.1080/15384047.2016.1139235
_version_ 1782429287661436928
author Kim, Eun Young
Cho, Eun Na
Park, Heae Surng
Hong, Ji Young
Lim, Seri
Youn, Jong Pil
Hwang, Seung Yong
Chang, Yoon Soo
author_facet Kim, Eun Young
Cho, Eun Na
Park, Heae Surng
Hong, Ji Young
Lim, Seri
Youn, Jong Pil
Hwang, Seung Yong
Chang, Yoon Soo
author_sort Kim, Eun Young
collection PubMed
description Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotinib, BH3 mimetics, MEK inhibitors, and PI3K-tyrosine kinase inhibitors, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (P = 0.001, independent sample t-test). Compound EGFR mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound EGFR mutations showed poor clinical outcomes, they should be closely monitored during follow-up.
format Online
Article
Text
id pubmed-4848002
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-48480022016-05-09 Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma Kim, Eun Young Cho, Eun Na Park, Heae Surng Hong, Ji Young Lim, Seri Youn, Jong Pil Hwang, Seung Yong Chang, Yoon Soo Cancer Biol Ther Research Paper Compound EGFR mutations, defined as double or multiple mutations in the EGFR tyrosine kinase domain, are frequently detected with advances in sequencing technology but its clinical significance is unclear. This study analyzed 61 cases of EGFR mutation positive lung adenocarcinoma using next-generation sequencing (NGS) based repeated deep sequencing panel of 16 genes that contain actionable mutations and investigated clinical implication of compound EGFR mutations. Compound EGFR mutation was detected in 15 (24.6%) of 61 cases of EGFR mutation-positive lung adenocarcinoma. The majority (12/15) of compound mutations are combination of the atypical mutation and typical mutations such as exon19 deletion, L858R or G719X substitutions, or exon 20 insertion whereas 3 were combinations of rare atypical mutations. The patients with compound mutation showed shorter overall survival than those with simple mutations (83.7 vs. 72.8 mo; P = 0.020, Breslow test). Among the 115 missense mutations discovered in the tested genes, a few number of actionable mutations were detected irrelevant to the subtype of EGFR mutations, including ALK rearrangement, BCL2L11 intron 2 deletion, KRAS c.35G>A, PIK3CA c.1633G>A which are possible target of crizotinib, BH3 mimetics, MEK inhibitors, and PI3K-tyrosine kinase inhibitors, respectively. 31 missense mutations were detected in the cases with simple mutations whereas 84 in those with compound mutation, showing that the cases with compound missense mutation have higher burden of missense mutations (P = 0.001, independent sample t-test). Compound EGFR mutations are detected at a high frequency using NGS-based repeated deep sequencing. Because patients with compound EGFR mutations showed poor clinical outcomes, they should be closely monitored during follow-up. Taylor & Francis 2016-01-19 /pmc/articles/PMC4848002/ /pubmed/26785607 http://dx.doi.org/10.1080/15384047.2016.1139235 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License http://creativecommons.org/licenses/by-nc/3.0/, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Research Paper
Kim, Eun Young
Cho, Eun Na
Park, Heae Surng
Hong, Ji Young
Lim, Seri
Youn, Jong Pil
Hwang, Seung Yong
Chang, Yoon Soo
Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title_full Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title_fullStr Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title_full_unstemmed Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title_short Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
title_sort compound egfr mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848002/
https://www.ncbi.nlm.nih.gov/pubmed/26785607
http://dx.doi.org/10.1080/15384047.2016.1139235
work_keys_str_mv AT kimeunyoung compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT choeunna compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT parkheaesurng compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT hongjiyoung compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT limseri compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT younjongpil compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT hwangseungyong compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma
AT changyoonsoo compoundegfrmutationisfrequentlydetectedwithcomutationsofactionablegenesandassociatedwithpoorclinicaloutcomeinlungadenocarcinoma