The distribution of the extrachromosomal DNA molecules in early lung cancer

Abstract Background Lung cancer (LC) is a cancer with high mortality worldwide. Research on the distribution and nature of extrachromosomal DNA molecules (EcDNAm) in early LC is scarce. Methods After removing linear DNA and mitochondrial circular DNA, EcDNAm were extracted from two paired LC tissue samples and amplified using rolling circle amplification. High throughput extrachromosomal DNA or RNA sequencing and bioinformatics analysis were used to explore the distribution and nature of the EcDNAm. To learn more about the role of oncogenes with large EcDNAm sizes, gene onology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Results RNA sequencing results revealed the significant difference in some genes between tumor and corresponding normal samples. At the same time, obvious distinctions were observed between relapsed and non-relapsed tumor samples. The nature of the EcDNAm was comparable between LC samples and matched normal samples. Compared with the matched normal samples, the number of EcDNAm with longer size (EcDNA), which contained driver oncogenes, was relatively high. The majority of EcDNA in this study was mainly focused on the tumor samples. Enrichment analysis of the cancer samples revealed enrichment in biological processes, such as positive regulation of protein localization, axon development and in utero embryonic development. Conclusions This study demonstrated the universality of the distribution and described the nature of EcDNAm in early LC. Moreover, our work fills the investigation of the EcDNAm gap and future studies should focus on the application of EcDNA as a potential biomarker in patients with early LC.