Detection of Structural Variations and Fusion Genes in Breast Cancer Samples Using Third-Generation Sequencing

Abstract

<b>Background:</b> Structural variations (SVs) are common genetic alterations in the human genome that could cause different phenotypes and diseases, including cancer. However, the detection of structural variations using the second-generation sequencing was limited by its short read length, which restrained our understanding of structural variations. <b>Methods:</b> In this study, we developed a 28-gene panel for long-read sequencing and employed it to Oxford Nanopore Technologies and Pacific Biosciences platforms. We analyzed structural variations in the 28 breast cancer-related genes through long-read genomic and transcriptomic sequencing of tumor, para-tumor, and blood samples in 19 breast cancer patients. <b>Results:</b> Our results showed that some somatic SVs were recurring among the selected genes, though the majority of them occurred in the non-exonic region. We found evidence supporting the existence of hotspot regions for SVs, which extended our previous understanding that they exist only for single nucleotide variations. <b>Conclusion:</b> In conclusion, we employed long-read genomic and transcriptomic sequencing to identify SVs from breast cancer patients and proved that this approach holds great potential in clinical application.