Mutational landscape of glomus tumor and clinical application of genomic profiling based on next-generation sequencing technology

Glomus tumor (GT) is a rare tumor with incompletely understood biological behavior and molecular genetic characteristics. This study aimed to comprehensively detect genetic mutations in GT using next-generation sequencing (NGS) and correlate these findings with clinical and pathological features to provide new insights into the pathogenesis and precision diagnosis of GT. A total of 171 somatic single nucleotide variants (SNVs) were identified in 44 GT samples, including 114 nonSynonymous_Substitution, 36 Intronic, 11 FrameShift_Duplication, 4 FrameShift_Deletion, 3 Splicing, and 3 Nonsense_Mutation events. The most frequent mutation type was G-A transition. Commonly mutated genes included BCL2L11, MUC16, KRAS, and BCR. Most copy number variations (CNVs) were losses; gains were observed only in CDK4 (4/44, 9.1 %) and CDK6 (3/44, 6.8 %) and were limited to benign and atypical GT. There is a significant correlation between high TMB and KRAS, TP53 mutations. Pathway enrichment analysis revealed KRAS mutations were predominant in distal GT, while BRAF V600E mutations were more prevalent in proximal locations. Atypical/malignant GTs may be associated with the epithelial-mesenchymal transition pathway. Tumor microenvironment gene typing in 51 GTs suggested a tendency for cold tumors to occur more frequently in male patients (P = 0.0686). This study represents the first comprehensive exploration of the molecular genetic characteristics of GT using NGS technology, which provides an initial overview of the genetic mutation landscape in GT.