Comprehensive Genomic Profiling of Sinonasal Carcinomas: Identification of Common Mutations and Potential Targets for Therapy

Abstract Sinonasal cancers are malignant neoplasms arising from the nasal cavity and paranasal sinuses, including squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma. Due to their rarity, comprehensive genomic data remain limited. Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. We analyzed sinonasal cancer cases from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database via cBioPortal (v16.1-public, accessed July 22, 2024). Common gene mutations, correlations, and mutual exclusivities were assessed using statistical analyses with false discovery rate correction. Of 2,595 head and neck cancer samples, 122 (4.7%) were sinonasal carcinoma: 70 (57.4%) SCC, 31 (25.4%) undifferentiated carcinoma, and 21 (17.2%) adenocarcinomas. The most frequent mutations were TP53 (tumor protein 53; 40%), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; 14%), KMT2D (lysine methyltransferase 2D; 11%), and CDKN2A (cyclin-dependent kinase inhibitor 2A; 9%). Subtype-specific mutations included IDH2 (isocitrate dehydrogenase; 230%) in undifferentiated carcinoma and FAT1 (15%) in adenocarcinoma. TP53 frequently co-occurred with PRKDC (protein kinase, DNA-activated, catalytic subunit; p = 0.020), while KMT2D co-occurred with PIK3CA (p = 0.018). TP53, PIK3CA, and KMT2D mutations are prevalent in sinonasal carcinoma, highlighting potential targets for therapy. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.