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

Abstract

Laryngeal squamous cell carcinoma (LSCC) is an aggressive cancer with poor quality of life. Understanding the somatic mutations in its genome can help us comprehend 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 shared across multiple samples - variants that play a crucial role in tumorigenesis. Here, we presented SomaGauss-SV, a somatic SVs detection workflow leveraging nanopore long-read sequencing data. Benchmarking against five paired tumor cell line datasets showed SomaGauss-SV consistently achieves a balanced high precision and recall. SomaGauss-SV applied to 15 paired LSCC tumor-blood samples uncovered a comprehensive SVs landscape and a significant positive correlation between somatic deletion burden and smoking intensity. Furthermore, a high-frequency somatic simple repeat expansion was identified in 28/39 (71.79%) of LSCC patients, upregulating 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.