Molecular Profiling of Olfactory Neuroblastoma Using the AACR Project GENIE Database

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/

Publikationsverlauf

Eingereicht: 19. April 2025

Angenommen: 17. Juni 2025

Accepted Manuscript online:
18. Juni 2025

Artikel online veröffentlicht:
27. Juni 2025

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