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integrative analysis of Genome,3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples

genomics, Proteomics & Bioinformatics 2021年第5期19卷 741-753页

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 Center for Bioinformatics School of Life SciencesCenter for Statistical SciencePeking UniversityBeijing 100871China BGI-Shenzhen Shenzhen 518083China Zhongshan Hospital Institute of Clinical Science Fudan UniversityShanghai Institute of Clinical BioinformaticsShanghai 200433China Fudan University Center for Clinical Bioinformatics Shanghai 200433China Department of Thoracic Surgery Zhongshan Hospital of Fudan UniversityShanghai 200032China School of Life Sciences Tsinghua UniversityBeijing 100084China BGI-Qingdao Qingdao 266426China Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics BGI-ShenzhenShenzhen 518083China iCarbonX Shenzhen 518053China Digital Life Research Institute Shenzhen 518110China State Key Laboratory of Proteomics National Center of Biomedical AnalysisInstitute of Basic Medical SciencesBeijing 100850China China National GeneBank BGI-ShenzhenShenzhen 518083China

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 ***,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical *** 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 *** 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 *** also showed that Hi-C data can be used to infer CNVs and point mutations in *** integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene *** propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin *** 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

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