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.

Details

Title
Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma
Author
Hu, Xin 1 ; Fujimoto, Junya 2 ; Ying, Lisha 3 ; Fukuoka, Junya 4 ; Ashizawa, Kazuto 5 ; Sun, Wenyong 6 ; Reuben, Alexandre 7   VIAFID ORCID Logo  ; Chi-Wan, Chow 2 ; McGranahan, Nicholas 8 ; Chen, Runzhe 7 ; Hu, Jinlin 6 ; Godoy, Myrna C 9 ; Tabata, Kazuhiro 4 ; Kuroda, Kishio 4 ; Shi, Lei 10 ; Li, Jun 1 ; Behrens, Carmen 7 ; Parra, Edwin Roger 2 ; Little, Latasha D 1 ; Gumbs, Curtis 1 ; Mao, Xizeng 1 ; Song, Xingzhi 1 ; Tippen, Samantha 1 ; Thornton, Rebecca L 1 ; Kadara, Humam 2 ; Scheet, Paul 11 ; Roarty, Emily 7 ; Ostrin, Edwin Justin 12   VIAFID ORCID Logo  ; Wang, Xu 10 ; Carter, Brett W 9 ; Antonoff, Mara B 13   VIAFID ORCID Logo  ; Zhang, Jianhua 1 ; Vaporciyan, Ara A 13 ; Pass, Harvey 14 ; Swisher, Stephen G 13   VIAFID ORCID Logo  ; Heymach, John V 7 ; Lee, J Jack 15   VIAFID ORCID Logo  ; Wistuba, Ignacio I 16 ; Hong, Waun Ki 7 ; Futreal, P Andrew 1 ; Su, Dan 6 ; Zhang, Jianjun 17 

1  Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
2  Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
3  Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital & Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, China 
4  Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 
5  Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 
6  Department of Pathology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China 
7  Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
8  Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence, London, UK 
9  Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
10  Department of Radiology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China 
11  Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
12  Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
13  Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
14  Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY, USA 
15  Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
16  Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
17  Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
Pages
1-10
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10877-8
ProQuest document ID
2252669499
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.