The Open Chromatin Landscape of Non-small Cell Lung Carcinoma

2019 
Non-small cell lung carcinoma (NSCLC) is a major cancer type whose epigenetic alteration remains unclear. We analyzed open chromatin data with matched whole-genome sequencing and RNA-seq data of 50 primary NSCLC cases. We observed high inter-patient heterogeneity of open chromatin profiles and the degree of heterogeneity correlated to several clinical parameters. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) exhibited distinct open chromatin patterns. Beyond this, we uncovered that the broadest open chromatin peaks indicated key NSCLC genes and led to less stable expression. Furthermore, we found that the open chromatin peaks were gained or lost together with somatic copy number alterations and affected the expression of important NSCLC genes. In addition, we identified 21 joint-QTLs that correlated to both ATAC-seq peak intensity and gene expression levels. Finally, we identified 87 regulatory risk loci associated with lung cancer-related phenotypes by intersecting the QTLs with GWAS significant loci. In summary, this compendium of multi-omics data provides valuable insights and a resource to understand the landscape of open chromatin features and regulatory networks in NSCLC.
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