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- Title
Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma.
- Authors
Hu, Xin; Fujimoto, Junya; Ying, Lisha; Fukuoka, Junya; Ashizawa, Kazuto; Sun, Wenyong; Reuben, Alexandre; Chow, Chi-Wan; McGranahan, Nicholas; Chen, Runzhe; Hu, Jinlin; Godoy, Myrna C.; Tabata, Kazuhiro; Kuroda, Kishio; Shi, Lei; Li, Jun; Behrens, Carmen; Parra, Edwin Roger; Little, Latasha D.; Gumbs, Curtis
- 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. There has been a drastic increase in detection of lung nodules, many of which are precancers, preinvasive, minimally invasive or sometimes invasive lung cancers. Here, Hu et al. perform multi-region exome sequencing to discern the evolutional trajectory from precancers to invasive lung cancers.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-10877-8