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J Neurol Surg B Skull Base
DOI: 10.1055/a-2639-5690
Original Article

Molecular Profiling of Olfactory Neuroblastoma Using the AACR Project GENIE Database

Beau Hsia
1   Department of Otolaryngology, Creighton University School of Medicine, Phoenix, Arizona, United States
,
Roshan Dongre
2   School of Engineering Medicine, Texas A&M University, Houston, Texas, United States
,
Aya Erquizi
3   Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States
,
Paula V. Guerra-Navarro
4   Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, United States
,
Gabriel Bitar
1   Department of Otolaryngology, Creighton University School of Medicine, Phoenix, Arizona, United States
,
Saif A. Alshaka
1   Department of Otolaryngology, Creighton University School of Medicine, Phoenix, Arizona, United States
,
Jeeho D. Kim
5   Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center San Diego, San Diego, California, United States
,
Bastien A. Valencia-Sanchez
6   Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic Florida, Jacksonville, Florida, United States
,
Michael G. Brandel
7   Department of Neurosurgery, University of California San Diego-Rady Children's Hospital, San Diego, California, United States
,
Mariko Sato
8   Department of Pediatric Oncology, Children's Hospital of Orange County, Orange, California, United States
,
John R. Crawford
9   Children's Hospital Orange County, University of California Irvine, Department of Pediatrics and Neurology, Orange, California, United States
,
Michael L. Levy
7   Department of Neurosurgery, University of California San Diego-Rady Children's Hospital, San Diego, California, United States
,
Vijay A. Patel
10   Division of Pediatric Otolaryngology, Rady Children's Hospital, San Diego, California, United States
11   Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States
,
Sean P. Polster
12   Department of Neurosurgery, University of Chicago, Chicago, Illinois, United States
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Abstract

Objective

Olfactory neuroblastoma (ONB) is a rare head and neck cancer arising from the upper nasal cavity, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to utilize a patient-level genomic repository to identify potential therapeutic targets and improve disease modeling in ONB.

Design

Retrospective genomic analysis.

Setting

Data analysis was performed using the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database.

Participants

Patients with confirmed ONB who have undergone targeted sequencing within GENIE.

Main Outcomes Measures

Data were analyzed for recurrent somatic mutations, along with their clinical and demographic correlations, with significance set at p < 0.05.

Results

A high prevalence of mutations in TP53 (tumor protein p53) and FRK (fibroblast growth factor receptor kinase) genes was identified. A moderate prevalence of mutations in NOTCH3 (notch receptor 3), SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4), RET (rearranged during transfection), and CTCF (CCCTC-binding factor) was also identified. The mutation patterns differed between pediatric and adult ONB cases. Specific mutations were enriched in metastatic tumors compared with primary tumors.

Conclusion

This study provides a genomic profile for ONB, identifying key mutations and potential therapeutic targets. The identification of frequently mutated genes like TP53 and FRK suggests potential targets for novel therapies. The observation that certain genes are mutated in pediatric ONB but not adult ONB (and vice versa), and the presence of specific mutations in metastatic tumors that are absent in primary tumors, offers valuable insights for future precision medicine and the design of targeted therapeutic interventions for these distinct clinical presentations.

Keywords

olfactory neuroblastoma - AACR Project GENIE - somatic mutations - TP53 - FRK - biomarker discovery - targeted therapy - cancer genomics

Previous Presentation

This study was presented at the NASBS Annual Meeting 2025 in New Orleans.


Authors' Contributions

The conceptualization of the study was led by V.A.P. The methodology was developed collaboratively by B.H., S.A.A., and G.B., while validation was carried out by B.H. and B.A.V-S. B.H. was responsible for formal analysis, data curation, and the preparation of the original draft. All authors contributed to the review and editing of the manuscript. Visualization was managed by B.H. and S.P. Supervision and project administration were undertaken by V.A.P. and S.P. All authors have read and approved the final version of the manuscript.


Institutional Review Board Statement

Ethical review and approval were waived for this study because the AACR Project GENIE is a publicly available cancer genomic database containing de-identified patient data, which minimizes potential risks to human subjects and eliminates the need 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: 19 April 2025

Accepted: 17 June 2025

Accepted Manuscript online:
18 June 2025

Article published online:
27 June 2025

© 2025. Thieme. All rights reserved.

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

 

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