Multiplatform discovery and regulatory function analysis of structural variations in non-small cell lung carcinoma

Lin Xia; Zhoufeng Wang; Xinyue Wu; Tianfu Zeng; Wenxin Luo; Xinlei Hu; Yinyun Ni; Guowei Che; Lunxu Liu; Wei Zhang; Dan Xie; Weimin Li

doi:10.1016/j.celrep.2021.109660

Multiplatform discovery and regulatory function analysis of structural variations in non-small cell lung carcinoma

Cell Rep. 2021 Sep 7;36(10):109660. doi: 10.1016/j.celrep.2021.109660.

Authors

Lin Xia¹, Zhoufeng Wang², Xinyue Wu¹, Tianfu Zeng¹, Wenxin Luo³, Xinlei Hu¹, Yinyun Ni⁴, Guowei Che⁵, Lunxu Liu⁵, Wei Zhang⁶, Dan Xie⁷, Weimin Li⁸

Affiliations

¹ Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, Sichuan 610041, China.
² Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, Sichuan 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China; The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China.
³ Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China.
⁴ Precision Medicine Research Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China.
⁵ Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China.
⁶ Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, the Second Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.
⁷ Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, Sichuan 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China. Electronic address: danxie@scu.edu.cn.
⁸ Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, Sichuan 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China; The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China. Electronic address: weimi003@scu.edu.cn.

PMID: 34496260
DOI: 10.1016/j.celrep.2021.109660

Abstract

Non-small cell lung carcinoma (NSCLC), the most common form of lung cancer, is the leading cause of cancer-related death worldwide. We perform whole-genome sequencing (WGS) on samples from 43 primary patients with NSCLC and matched normal samples and analyze their matched open chromatin data and transcriptome data. Our results indicate that next-generation sequencing (NGS) and the Bionano Genomics (BNG) platform should be viewed as complementary technologies in terms of structural variations detection. By creating a framework integrating these two platforms, we detect high-technical-confidence somatic structural variations (SVs) in NSCLC cases, which could aid in the efficient investigation of new candidate oncogenes, such as TRIO and SESTD1. Our findings highlight the impact of somatic SVs on NSCLC oncogenesis and lay a foundation for exploring associations among somatic SVs, gene expression, and regulatory networks in patients with NSCLC.

Keywords: Bionano Genomics platform; multisequencing platforms; non-small cell lung carcinoma; regulatory network; structural variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology*
Genome, Human / genetics
Genomics / methods
High-Throughput Nucleotide Sequencing / methods
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism*
Mutation / genetics
Oncogenes / genetics
Whole Genome Sequencing / methods