Format

Send to

Choose Destination
Nat Commun. 2019 Jul 5;10(1):2978. doi: 10.1038/s41467-019-10877-8.

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

Author information

1
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
2
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, 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, 310022, Hangzhou, China.
4
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 8528523, Nagasaki, Japan.
5
Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 8528523, 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, 310022, Hangzhou, China.
7
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
8
Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence, London, WC1E6BT, UK.
9
Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, 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, 310022, Hangzhou, China.
11
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
12
Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
13
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
14
Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY, 10016, USA.
15
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
16
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. afutreal@mdanderson.org.
17
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, 310022, Hangzhou, China. sudan@zjcc.org.cn.
18
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jzhang20@mdanderson.org.
19
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jzhang20@mdanderson.org.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center