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Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing

Background: Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of pr...

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Autores principales: Li, Dingbiao, Huang, Yong, Cai, Lijun, Wu, Min, Bao, Hua, Xu, Yang, Wei, Yulin, Wu, Shuyu, Wu, Xue, Shao, Yang, Zhao, Wei, Lv, Guoli, Huang, Shan, Zhang, Tao, Shi, Yunfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571538/
https://www.ncbi.nlm.nih.gov/pubmed/34735995
http://dx.doi.org/10.1016/j.neo.2021.10.001
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author Li, Dingbiao
Huang, Yong
Cai, Lijun
Wu, Min
Bao, Hua
Xu, Yang
Wei, Yulin
Wu, Shuyu
Wu, Xue
Shao, Yang
Zhao, Wei
Lv, Guoli
Huang, Shan
Zhang, Tao
Shi, Yunfei
author_facet Li, Dingbiao
Huang, Yong
Cai, Lijun
Wu, Min
Bao, Hua
Xu, Yang
Wei, Yulin
Wu, Shuyu
Wu, Xue
Shao, Yang
Zhao, Wei
Lv, Guoli
Huang, Shan
Zhang, Tao
Shi, Yunfei
author_sort Li, Dingbiao
collection PubMed
description Background: Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of precision medicine. Methods: We performed retrospective analyses on targeted sequencing data of 3,743 primary tumors and 934 metastases from 4,480 patients with lung adenocarcinomas, and PD-L1 immunohistochemical data of 1,336 primary tumors and 252 metastases from 1,588 LUAD patients. Results: Metastases generally manifested significantly higher mutational burdens and chromosomal instability than primary lung adenocarcinomas. Clinically actionable alterations, including ALK mutations, ALK and ROS1 fusions, and MET copy number gains, were enriched in metastases, particularly metastases to some specific organs/tissues, such as lymph nodes, liver, and brain. PD-L1 expression decreased as the approximate metastatic distance increased. Additional data of paired primary tumors and metastases to lymph nodes and brain validated patterns of actionable alterations and candidates for metastatic drivers. Two evolutionary modes of metastatic dissemination, common origins and distinct origins, were identified in both types of primary-metastasis pairs. Conclusions: Our study showed heterogenous patterns of clinically actionable alterations, PD-L1 expressions, metastatic driver candidates, and evolutionary patterns among multiple types of metastases of lung adenocarcinomas, which may advise the planning of treatments and the identification of novel therapeutic targets.
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spelling pubmed-85715382021-11-19 Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing Li, Dingbiao Huang, Yong Cai, Lijun Wu, Min Bao, Hua Xu, Yang Wei, Yulin Wu, Shuyu Wu, Xue Shao, Yang Zhao, Wei Lv, Guoli Huang, Shan Zhang, Tao Shi, Yunfei Neoplasia Original article Background: Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of precision medicine. Methods: We performed retrospective analyses on targeted sequencing data of 3,743 primary tumors and 934 metastases from 4,480 patients with lung adenocarcinomas, and PD-L1 immunohistochemical data of 1,336 primary tumors and 252 metastases from 1,588 LUAD patients. Results: Metastases generally manifested significantly higher mutational burdens and chromosomal instability than primary lung adenocarcinomas. Clinically actionable alterations, including ALK mutations, ALK and ROS1 fusions, and MET copy number gains, were enriched in metastases, particularly metastases to some specific organs/tissues, such as lymph nodes, liver, and brain. PD-L1 expression decreased as the approximate metastatic distance increased. Additional data of paired primary tumors and metastases to lymph nodes and brain validated patterns of actionable alterations and candidates for metastatic drivers. Two evolutionary modes of metastatic dissemination, common origins and distinct origins, were identified in both types of primary-metastasis pairs. Conclusions: Our study showed heterogenous patterns of clinically actionable alterations, PD-L1 expressions, metastatic driver candidates, and evolutionary patterns among multiple types of metastases of lung adenocarcinomas, which may advise the planning of treatments and the identification of novel therapeutic targets. Neoplasia Press 2021-11-01 /pmc/articles/PMC8571538/ /pubmed/34735995 http://dx.doi.org/10.1016/j.neo.2021.10.001 Text en © 2021 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Li, Dingbiao
Huang, Yong
Cai, Lijun
Wu, Min
Bao, Hua
Xu, Yang
Wei, Yulin
Wu, Shuyu
Wu, Xue
Shao, Yang
Zhao, Wei
Lv, Guoli
Huang, Shan
Zhang, Tao
Shi, Yunfei
Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title_full Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title_fullStr Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title_full_unstemmed Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title_short Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
title_sort genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571538/
https://www.ncbi.nlm.nih.gov/pubmed/34735995
http://dx.doi.org/10.1016/j.neo.2021.10.001
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