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:	Dingbiao Li, Yong Huang, Lijun Cai, Min Wu, Hua Bao, Yang Xu, Yulin Wei, Shuyu Wu, Xue Wu, Yang Shao, Wei Zhao, Guoli Lv, Shan Huang, Tao Zhang, Yunfei Shi
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Genomic profiling NSCLC Metastasis Therapeutic target Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/71e416327832450e9c08d15bd8d099a3
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spelling	oai:doaj.org-article:71e416327832450e9c08d15bd8d099a32021-11-30T04:14:35ZGenomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing1476-558610.1016/j.neo.2021.10.001https://doaj.org/article/71e416327832450e9c08d15bd8d099a32021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621000865https://doaj.org/toc/1476-5586Background: 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.Dingbiao LiYong HuangLijun CaiMin WuHua BaoYang XuYulin WeiShuyu WuXue WuYang ShaoWei ZhaoGuoli LvShan HuangTao ZhangYunfei ShiElsevierarticleGenomic profilingNSCLCMetastasisTherapeutic targetNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1204-1212 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genomic profiling NSCLC Metastasis Therapeutic target Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Genomic profiling NSCLC Metastasis Therapeutic target Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Dingbiao Li Yong Huang Lijun Cai Min Wu Hua Bao Yang Xu Yulin Wei Shuyu Wu Xue Wu Yang Shao Wei Zhao Guoli Lv Shan Huang Tao Zhang Yunfei Shi Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
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.
format	article
author	Dingbiao Li Yong Huang Lijun Cai Min Wu Hua Bao Yang Xu Yulin Wei Shuyu Wu Xue Wu Yang Shao Wei Zhao Guoli Lv Shan Huang Tao Zhang Yunfei Shi
author_facet	Dingbiao Li Yong Huang Lijun Cai Min Wu Hua Bao Yang Xu Yulin Wei Shuyu Wu Xue Wu Yang Shao Wei Zhao Guoli Lv Shan Huang Tao Zhang Yunfei Shi
author_sort	Dingbiao Li
title	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_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_sort	genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/71e416327832450e9c08d15bd8d099a3
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Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing

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