• Chao Zhang, Jianjun Zhang, Fang-Ping Xu, Yin-Guang Wang, Zhi Xie, Jian Su, Song Dong, Qiang Nie, Yang Shao, Qing Zhou, Jin-Ji Yang, Xue-Ning Yang, Xu-Chao Zhang, Zhi Li, Yi-Long Wu, and Wen-Zhao Zhong.
• Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China; School of Medicine, South China University of Technology, Guangzhou, People's Republic of China.
• J Thorac Oncol. 2019 Nov 1; 14 (11): 1912-1923.

BackgroundUnderstanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention.MethodsA total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1).ResultsAll tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 expression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations.ConclusionsMutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion.Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

34 keywords...

hide…