• Xin Hu, Junya Fujimoto, Lisha Ying, Junya Fukuoka, Kazuto Ashizawa, Wenyong Sun, Alexandre Reuben, Chi-Wan Chow, Nicholas McGranahan, Runzhe Chen, Jinlin Hu, Myrna C Godoy, Kazuhiro Tabata, Kishio Kuroda, Lei Shi, Jun Li, Carmen Behrens, Edwin Roger Parra, Latasha D Little, Curtis Gumbs, Xizeng Mao, Xingzhi Song, Samantha Tippen, Rebecca L Thornton, Humam Kadara, Paul Scheet, Emily Roarty, Edwin Justin Ostrin, Xu Wang, Brett W Carter, Mara B Antonoff, Jianhua Zhang, Ara A Vaporciyan, Harvey Pass, Stephen G Swisher, John V Heymach, J Jack Lee, Ignacio I Wistuba, Waun Ki Hong, Futreal P Andrew PA Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. afutreal@mdanderson.org., Dan Su, and Jianjun Zhang.
• Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
• Nat Commun. 2019 Jul 5; 10 (1): 2978.

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.

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