Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma
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Published:2019-07-05
Issue:1
Volume:10
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Hu Xin, Fujimoto Junya, Ying Lisha, Fukuoka Junya, Ashizawa Kazuto, Sun Wenyong, Reuben AlexandreORCID, Chow Chi-Wan, McGranahan Nicholas, Chen Runzhe, Hu Jinlin, Godoy Myrna C., Tabata Kazuhiro, Kuroda Kishio, Shi Lei, Li Jun, Behrens Carmen, Parra Edwin Roger, Little Latasha D., Gumbs Curtis, Mao Xizeng, Song Xingzhi, Tippen Samantha, Thornton Rebecca L., Kadara Humam, Scheet Paul, Roarty Emily, Ostrin Edwin JustinORCID, Wang Xu, Carter Brett W., Antonoff Mara B.ORCID, Zhang Jianhua, Vaporciyan Ara A., Pass Harvey, Swisher Stephen G.ORCID, Heymach John V., Lee J. JackORCID, Wistuba Ignacio I., Hong Waun Ki, Futreal P. Andrew, Su Dan, Zhang Jianjun
Abstract
AbstractThere has been a dramatic increase in the detection of lung nodules, many of which are preneoplasia atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (ADC). The molecular landscape and the evolutionary trajectory of lung preneoplasia have not been well defined. Here, we perform multi-region exome sequencing of 116 resected lung nodules including AAH (n = 22), AIS (n = 27), MIA (n = 54) and synchronous ADC (n = 13). Comparing AAH to AIS, MIA and ADC, we observe progressive genomic evolution at the single nucleotide level and demarcated evolution at the chromosomal level supporting the early lung carcinogenesis model from AAH to AIS, MIA and ADC. Subclonal analyses reveal a higher proportion of clonal mutations in AIS/MIA/ADC than AAH suggesting neoplastic transformation of lung preneoplasia is predominantly associated with a selective sweep of unfit subclones. Analysis of multifocal pulmonary nodules from the same patients reveal evidence of convergent evolution.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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