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J Neurol Surg B Skull Base
DOI: 10.1055/a-2639-5790
Original Article

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

Gabriel Bitar
1   School of Medicine, Creighton University, Phoenix, Arizona, United States
,
Beau Hsia 
1   School of Medicine, Creighton University, Phoenix, Arizona, United States
,
Saif Alshaka
1   School of Medicine, Creighton University, Phoenix, Arizona, United States
,
Bastien A. Valencia
2   Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic Florida, Jacksonville, Florida, United States
,
Jeeho Kim
3   Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center San Diego, San Diego, California, United States
,
Mariko Sato
4   Department of Pediatric Oncology, Children's Hospital of Orange County, Orange, California, United States
,
John Crawford
5   Children's Hospital Orange County, University of California Irvine, Department of Pediatrics and Neurology, Orange, California, United States
,
Michael L. Levy
6   Department of Neurosurgery, University of California San Diego-Rady Children's Hospital, San Diego, California, United States
,
Sean Polster
7   Department of Neurosurgery, University of Chicago, Chicago, Illinois, United States
,
Vijay A. Patel
8   Division of Pediatric Otolaryngology, Rady Children's Hospital, San Diego, California, United States
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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

Institutional Review Board Statement

Ethical review and approval were waived for this study because the AACR Project GENIE is a publicly accessible cancer genomic database that contains deidentified patient data, thereby reducing potential risks to human subjects and eliminating the requirement for individual participant consent.


Data Availability Statement

The data presented in this study are available from the AACR GENIE database at https://genie.cbioportal.org/.




Publication History

Received: 22 April 2025

Accepted: 17 June 2025

Accepted Manuscript online:
18 June 2025

Article published online:
02 July 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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