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bioRxiv · 10.1101/2023.10.07.561149

Landscape of Large-Scale Somatic Genomic Insertions in Non-Small Cell Lung Carcinoma Revealed by Nanopore Sequencing

Xie, D.·Xia, L.·Wang, Z.·Zeng, T.·Wang, H.·PI, X.·Zhu, G.·Wu, X.·Li, Y.·Den, Y.·Qi, Y.·Liu, X.·Zhang, F.·Li, W.
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Abstract

Previous NSCLC genomic studies were mostly based on the next-generation sequencing of short reads, which is an efficient approach for identifying single nucleotide variants and small indels but ineffective for identifying structural variants, especially large-scale insertions. Here, we studied 151 lung adenocarcinoma (LUAD) and 106 lung squamous cell carcinoma (LUSC) samples and paired blood samples using nanopore sequencing technology. We developed a rigorous computational pipeline and characterized the landscape of large-scale somatic insertions in NSCLC. Combining other omics data, we report three findings: 1. we identified an LUSC-enriched somatic simple repeat expansion shared by approximately 40% of LUSC patients that regulates PTPRZ1 gene expression through distal enhancers; 2. the somatic insertion of transposable elements (TEs) in NSCLC were mostly complex TEs consisting of multiple TE elements; and 3. the insertion of short interspersed nuclear elements, especially from the Alu family in young lineages, is a frequent somatic mutation type that shapes the transcriptome of NSCLC through the expression of these elements.

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Xie, D., Xia, L., Wang, Z., Zeng, T., Wang, H., PI, X., Zhu, G., Wu, X., Li, Y., Den, Y., Qi, Y., Liu, X., Zhang, F., Li, W.. 2023-10-10. Landscape of Large-Scale Somatic Genomic Insertions in Non-Small Cell Lung Carcinoma Revealed by Nanopore Sequencing. https://doi.org/10.1101/2023.10.07.561149

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