Whole Genome Sequencing of Sporadic Vestibular Schwannoma Reveals Novel Genetic Changes.

HYPOTHESIS: Whole-genome sequencing of sporadic vestibular schwannoma (VS) specimens will reveal novel genetic mutations and molecular pathways involved in the pathogenesis of the disease.

BACKGROUND

The optimal treatment for VS remains uncertain due to the inability to predict tumor behavior, growth, and symptom progression. While molecular changes and mutational burden may govern tumor behavior, genotype-phenotype correlations are not well established. The objective of this study was to describe the genomic landscape of sporadic VS utilizing next-generation sequencing, namely whole-genome sequencing (WGS), to identify novel genes and pathways involved in tumor behavior.

METHODS

Tumor and matched peripheral whole blood specimens were collected from 28 patients with pathologically confirmed VS who underwent surgical resection. Demographic and clinical characteristics were obtained. Specimens were stratified by pre-operative hearing status, macrocystic change, and growth behavior. Whole-genome sequencing was performed on 23 specimens. Quality control, somatic variant calling, differential expression, and functional enrichment analysis were completed.

RESULTS

Whole-genome sequencing revealed 46 genes mutated in 4 or more tumor samples. Genes including ADGRV1, OTOGL, TRIOBP, APC, and MUC genes were identified to be of particular relevance. CAPN5 and NRP2 were downregulated in tumors with cystic change. The NF2 gene was affected in 16 of 23 samples, with 32 identified mutations.

CONCLUSION

Next-generation sequencing of sporadic vestibular schwannoma specimens identified numerous novel mutated genes and differentially expressed proteins, which may be important drivers of tumor behavior and pathogenesis.