Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Xin Hu(The University of Texas MD Anderson Cancer Center), Junya Fujimoto(The University of Texas MD Anderson Cancer Center), Lisha Ying(Zhejiang Cancer Hospital), Junya Fukuoka(Nagasaki University), Kazuto Ashizawa(Nagasaki University), Wenyong Sun(Zhejiang Cancer Hospital), Alexandre Reuben(The University of Texas MD Anderson Cancer Center), Chi-Wan Chow(The University of Texas MD Anderson Cancer Center), Nicholas McGranahan(CRUK Lung Cancer Centre of Excellence), Runzhe Chen(The University of Texas MD Anderson Cancer Center), Jinlin Hu(Zhejiang Cancer Hospital), Myrna C.B. Godoy(The University of Texas MD Anderson Cancer Center), Kazuhiro Tabata(Nagasaki University), Kishio Kuroda(Nagasaki University), Lei Shi(Zhejiang Cancer Hospital), Jun Li(The University of Texas MD Anderson Cancer Center), Carmen Behrens(The University of Texas MD Anderson Cancer Center), Edwin R. Parra(The University of Texas MD Anderson Cancer Center), Latasha Little(The University of Texas MD Anderson Cancer Center), Curtis Gumbs(The University of Texas MD Anderson Cancer Center), Xizeng Mao(The University of Texas MD Anderson Cancer Center), Xingzhi Song(The University of Texas MD Anderson Cancer Center), Samantha Tippen(The University of Texas MD Anderson Cancer Center), Rebecca Thornton(The University of Texas MD Anderson Cancer Center), Humam Kadara(The University of Texas MD Anderson Cancer Center), Paul Scheet(The University of Texas MD Anderson Cancer Center), Emily Roarty(The University of Texas MD Anderson Cancer Center), Edwin J. Ostrin(The University of Texas MD Anderson Cancer Center), Xu Wang(Zhejiang Cancer Hospital), Brett W. Carter(The University of Texas MD Anderson Cancer Center), Mara B. Antonoff(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), Ara A. Vaporciyan(The University of Texas MD Anderson Cancer Center), Harvey I. Pass(NYU Langone Health), Stephen G. Swisher(The University of Texas MD Anderson Cancer Center), John V. Heymach(The University of Texas MD Anderson Cancer Center), J. Jack Lee(The University of Texas MD Anderson Cancer Center), Ignacio I. Wistuba(The University of Texas MD Anderson Cancer Center), Waun Ki Hong(The University of Texas MD Anderson Cancer Center), P. Andrew Futreal(The University of Texas MD Anderson Cancer Center), Dan Su(Zhejiang Cancer Hospital), Jianjun Zhang(The University of Texas MD Anderson Cancer Center)
Nature Communications
July 5, 2019
10.1038/s41467-019-10877-8
Cited by 186Open Access
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Abstract

There 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.

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