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Comprehensive Genomic Profiling of Sinonasal Carcinomas: Identification of Common Mutations and Potential Targets for
Gabriel Bitar1, Beau Hsia1, Saif Alshaka1
1School of Medicine, Creighton University, Phoenix, Arizona, United States.
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.
Insights
Genomic analysis of sinonasal cancers reveals frequent TP53, PIK3CA, and KMT2D mutations. These findings suggest potential therapeutic targets, including DNA methylation and PIK3CA signaling pathways, for improved treatment strategies.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Sinonasal cancers are rare malignant neoplasms.
- Comprehensive genomic data are limited due to their rarity.
- Current treatments include surgery, radiation, and chemotherapy, with ongoing trials for novel agents.
Purpose of the Study:
- To analyze genomic alterations in sinonasal carcinoma.
- To identify common gene mutations, correlations, and mutual exclusivities.
- To explore potential therapeutic targets based on mutation profiles.
Main Methods:
- Analysis of 122 sinonasal cancer cases from the AACR GENIE database via cBioPortal.
- Statistical analyses with false discovery rate correction to assess gene mutations, correlations, and mutual exclusivities.
Main Results:
- TP53 (40%), PIK3CA (14%), KMT2D (11%), and CDKN2A (9%) were the most frequent mutations.
- Subtype-specific mutations included IDH2 in undifferentiated carcinoma and FAT1 in adenocarcinoma.
- TP53 co-occurred with PRKDC, and KMT2D co-occurred with PIK3CA.
Conclusions:
- TP53, PIK3CA, and KMT2D mutations are prevalent in sinonasal carcinoma.
- These mutations represent potential therapeutic targets.
- Targeted therapies like Tazemetostat and cetuximab may offer benefits, warranting further research.
