Abstract

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

Details

Title
Genomic and immune profiling of pre-invasive lung adenocarcinoma
Author
Chen, Haiquan 1 ; Carrot-Zhang, Jian 2   VIAFID ORCID Logo  ; Zhao, Yue 3 ; Hu, Haichuan 3 ; Freeman, Samuel S 2 ; Su, Yu 3 ; Ha, Gavin 4   VIAFID ORCID Logo  ; Taylor, Alison M 2 ; Berger, Ashton C 5 ; Westlake, Lindsay 5 ; Zheng, Yuanting 6 ; Zhang, Jiyang 6 ; Ramachandran, Aruna 7 ; Zheng, Qiang 8 ; Pan, Yunjian 3 ; Zheng, Difan 3 ; Zheng, Shanbo 3 ; Cheng, Chao 3 ; Kuang, Muyu 3 ; Zhou, Xiaoyan 8 ; Zhang, Yang 3 ; Li, Hang 3 ; Ye, Ting 3 ; Ma, Yuan 3 ; Gao, Zhendong 3 ; Tao, Xiaoting 3 ; Han, Han 3 ; Shang, Jun 6   VIAFID ORCID Logo  ; Yu, Ying 6 ; Ding, Bao 6 ; Huang, Yechao 6 ; Li, Xiangnan 6 ; Zhang, Yawei 3 ; Xiang, Jiaqing 3 ; Sun, Yihua 3 ; Li, Yuan 8 ; Cherniack, Andrew D 7   VIAFID ORCID Logo  ; Campbell, Joshua D 9 ; Shi, Leming 6 ; Meyerson, Matthew 2   VIAFID ORCID Logo 

1  Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China 
2  Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA 
3  Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 
4  Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 
5  Broad Institute of MIT and Harvard, Cambridge, MA, USA 
6  State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China 
7  Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA 
8  Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 
9  Division of Computational Biomedicine, Department of Medicine, Boston University, Boston, MA, USA 
Pages
1-6
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13460-3
ProQuest document ID
2319732000
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.