Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples.
Genomics Proteomics Bioinformatics
; 19(5): 741-753, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34116262
ABSTRACT
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 × 104), 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Pulmao
Base de dados:
MEDLINE
Assunto principal:
Variações do Número de Cópias de DNA
/
Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Genomics Proteomics Bioinformatics
Assunto da revista:
BIOQUIMICA
/
GENETICA
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INFORMATICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China