Tumor evolutionary trajectories during the acquisition of invasiveness in early stage lung adenocarcinoma

Siwei Wang, Mulong Du, Jingyuan Zhang, Weizhang Xu, Qianyu Yuan, Ming Li, Jie Wang, Hongyu Zhu, Yuzhuo Wang, Cheng Wang, Yuhua Gong, Xiaonan Wang, Zhibin Hu, David C. Christiani, Lin Xu, Hongbing Shen and Rong Yin ()
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Siwei Wang: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Mulong Du: Nanjing Medical University
Jingyuan Zhang: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Weizhang Xu: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Qianyu Yuan: Harvard T. H. Chan School of Public Health
Ming Li: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Jie Wang: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Hongyu Zhu: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Yuzhuo Wang: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Cheng Wang: Nanjing Medical University
Yuhua Gong: Geneplus-Beijing Institute
Xiaonan Wang: Geneseeq-Nanjing Technology Inc.
Zhibin Hu: Nanjing Medical University
David C. Christiani: Harvard T. H. Chan School of Public Health
Lin Xu: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research
Hongbing Shen: Nanjing Medical University
Rong Yin: Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: Abstract The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.

Date: 2020
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DOI: 10.1038/s41467-020-19855-x

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