Abstract
Objective
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.
Materials and Methods
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.
Results
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).
Conclusion
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.
Keywords
sinonasal carcinoma - genomic profiling - TP53 mutation - PIK3CA mutation - PI3K/AKT
pathway - targeted therapies - precision oncology - epigenetic modulation
