Integrative Analysis of Genome,3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples  

作　　者：Tingting Li Ruifeng Li Xuan Dong Lin Shi Miao Lin Ting Peng Pengze Wu Yuting Liu Xiaoting Li Xuheng He Xu Han Bin Kang Yinan Wang Zhiheng Liu Qing Chen Yue Shen Mingxiang Feng Xiangdong Wang Duojiao Wu Jian Wang Cheng Li 

机构地区：[1]Center for Bioinformatics,School of Life Sciences,Center for Statistical Science,Peking University,Beijing 100871,China [2]BGI-Shenzhen,Shenzhen 518083,China [3]Zhongshan Hospital Institute of Clinical Science,Fudan University,Shanghai Institute of Clinical Bioinformatics,Shanghai 200433,China [4]Fudan University Center for Clinical Bioinformatics,Shanghai 200433,China [5]Department of Thoracic Surgery,Zhongshan Hospital of Fudan University,Shanghai 200032,China [6]School of Life Sciences,Tsinghua University,Beijing 100084,China [7]BGI-Qingdao,Qingdao 266426,China [8]Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics,BGI-Shenzhen,Shenzhen 518083,China [9]iCarbonX,Shenzhen 518053,China [10]Digital Life Research Institute,Shenzhen 518110,China [11]State Key Laboratory of Proteomics,National Center of Biomedical Analysis,Institute of Basic Medical Sciences,Beijing 100850,China [12]China National GeneBank,BGI-Shenzhen,Shenzhen 518083,China

出　　处：《Genomics, Proteomics & Bioinformatics》2021年第5期741-753,共13页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.31871266);the National Key R&D Program of China(Grant No.2016YFA0100103);the National Natural Science Foundation of China Key Research Grant(Grant No.71532001);supported by funding from Shenzhen Municipal Government of China(Grant No.DRC-SZ[2016]884)。

摘　　要：Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clinical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×10^(4)),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer samples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

关 键 词：Lung cancer 3D genome Copy number variation Clinical sample Integrative genomic analysis 

分 类 号：R734.2[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]