Genomic landscape of schwannomas: An analysis of somatic mutations and demographic disparities

Schwannomas are typically benign nerve sheath tumors characterized by mutations in the NF2 gene. However, the complete genomic landscape, especially across diverse patient populations, remains incompletely understood. This study aims to provide a comprehensive analysis of the somatic mutations in schwannomas, with a focus on identifying demographic-specific genetic alterations. We analyzed genomic and clinical data from 248 patients with schwannomas using the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. We investigated the frequency of somatic mutations and copy number alterations and performed statistical analyses to identify significant associations with sex and race. Our analysis confirmed that NF2 is the most frequently mutated gene in schwannomas (51.6%). Other commonly mutated genes included SOX10 (7.66%), FAT1 (6.45%), SMARCB1 (5.65%), and LZTR1 (5.65%). We identified significant sex-specific mutational patterns, with BRCA2 and FANCA mutations more prevalent in females, while mutations in FGFR4 , FLCN , and KIT were more common in males. Furthermore, several mutations, including ROS1 , NSD1 , and FAT1 , were found to be significantly more frequent in Asian patients. We also observed a significant co-occurrence of mutations in ARID1A and SMARCB1 . This study confirms the central role of NF2 in schwannoma pathogenesis and uncovers novel, demographically distinct mutational signatures. The identification of sex- and race-specific genetic alterations, along with the co-occurrence of mutations in chromatin remodeling genes, provides deeper insights into the molecular heterogeneity of schwannomas. These findings may inform the development of more personalized diagnostic and therapeutic strategies for patients with this tumor.