Open Chromatin Landscape of non-small Cell Lung Carcinoma

Open chromatin landscape data with matched whole-genome sequencing and RNA-seq data of primary NSCLC cases

Summary

We analyzed open chromatin landscape 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. We identified sub-types of LUAD samples using open chromatin profile, which were associated with tumor stage. Beyond this, we uncovered that the broadest open chromatin peaks indicated key NSCLC genes and led to less stable expression of these genes. Furthermore, we found that the open chromatin peaks were gained or lost together with somatic copy number alterations and affected gene expression of important NSCLC genes. In addition, we identified 21 joint-QTLs that correlated to both ATAC-seq peak intensity and gene expression levels in our samples, which were potential regulatory loci involved in the gene regulatory network of NSCLC. Finally, we identified 87 regulatory risk loci associated with multiple lung cancer related phenotypes by intersecting the QTLs with GWAS significant loci.

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Data Access

Matched ATAC-seq, DNA-seq and RNA-seq datasets from primary NSCLC cases could be accessed through data portal.

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