Abstract 5377: Tracking genomic and epigenomic evolution from preneoplastic lesions to lung adenocarcinoma by multiregion sequencing

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.5377-5377
• Main Authors: Hu, Xin, Fujimoto, Junya, Ying, Lisha, Chen, Runzhe, Estecio, Marcos Roberto, Chow, Chi-Wan, Canales, Jaime Rodriguez, Song, Xingzhi, Mao, Xizeng, Scheet, Paul, Kadara, Humam, Cuentas, Edwin R. Parra Cuentas, Behrens, Carmen, Wu, Chang-Jiun, Lee, J. Jack, Antonoff, Mara, Vaporciyan, Ara A, Swisher, Stephen, zhang, Jianhua, Heymach, John, Hong, Waun Ki, Wistuba, Ignacio I., Sun, Wenyong, Hu, Jinlin, Futreal, P. Andrew, Su, Dan, Zhang, Jianjun
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-5377

Background: Carcinogenesis may result from accumulation of genomic and epigenomic aberrations. It has been postulated that atypical adenomatous hyperplasia (AAH) represents lung preneoplastic lesion that may progress to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and further to frankly invasive adenocarcinoma (ADC). Yet the pathologic definition and management of these lesions remain controversial due to lack of sufficient molecular evidences. This aim of this study is to delineate the temporal molecular carcinogenetic events and evolutionary process during the evolution from preneoplastic lesions to early-stage adenocarcinoma. Methods: We have collected 116 resected pre- and early neoplastic lung lesions including AAH (N=22), AIS (N=27), MIA (N=54) and ADC (N=13) from 53 patients, including 39 patients presenting with multifocal disease and 23 patients carrying more than two different types of lesions. Two to five spatially separated regions were subjected to whole-exome sequencing and reduced representation bisulfite sequencing. Results: Mutation burden progressively increases from AAH (average SNVs 0.57/Mb) to AIS (2.04/MB), to MIA (2.98/MB) and ADC (5.4/MB), p