Nanopore sequencing identifies high-frequency somatic structural variations in laryngeal squamous cell carcinoma...

Laryngeal squamous cell carcinoma (LSCC) is an aggressive cancer associated with poor quality of life. Understanding the somatic mutations in its genome is crucial for elucidating its occurrence and progression. Although somatic structural variations (SVs) have been documented in LSCC, conventional short-read sequencing lacks the sensitivity to effectively detect high-frequency SVs, variants that play a crucial role in tumorigenesis, shared across multiple samples. Here, we present SomaGauss-SV, a somatic SV detection workflow leveraging nanopore long-read sequencing data. Benchmarking against five paired tumor cell line data sets shows SomaGauss-SV consistently achieves a balanced high precision and recall. SomaGauss-SV applied to 15 paired LSCC tumor-blood samples uncovers a comprehensive SV landscape and reveals a significant positive correlation between somatic deletion burden and smoking intensity. Furthermore, a high-frequency somatic simple repeat expansion is identified in 28/39 (71.79%) of LSCC patients, which upregulates the expression of genes TP53BP2 and FBXO28 through spatial proximity. These findings underscore the potential of long-read sequencing and SomaGauss-SV for uncovering recurrent somatic SVs in LSCC, providing valuable resources for biomarker discovery.