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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.

2023-10-10 genomics
10.1101/2023.10.07.561149 bioRxiv
Show 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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