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Updated: May 21, 2026
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
Paired tumor and normal whole genome sequencing of metastatic olfactory neuroblastoma
Glen J Weiss1, Winnie S Liang, Tyler Izatt
1Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare (VGPCC), Scottsdale, Arizona, United States of America. gweiss@tgen.org
Background:
Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal tract with little molecular characterization. We performed whole genome sequencing (WGS) on paired normal and tumor DNA from a patient with metastatic-ONB to identify the somatic alterations that might be drivers of tumorigenesis and/or metastatic progression.
Methodology/Principal Findings:
Genomic DNA was isolated from fresh frozen tissue from a metastatic lesion and whole blood, followed by WGS at >30X depth, alignment and mapping, and mutation analyses. Sanger sequencing was used to confirm selected mutations. Sixty-two somatic short nucleotide variants (SNVs) and five deletions were identified inside coding regions, each causing a non-synonymous DNA sequence change. We selected seven SNVs and validated them by Sanger sequencing. In the metastatic ONB samples collected several months prior to WGS, all seven mutations were present. However, in the original surgical resection specimen (prior to evidence of metastatic disease), mutations in KDR, MYC, SIN3B, and NLRC4 genes were not present, suggesting that these were acquired with disease progression and/or as a result of post-treatment effects.
Conclusions/Significance:
This work provides insight into the evolution of ONB cancer cells and provides a window into the more complex factors, including tumor clonality and multiple driver mutations.
Insights
Whole genome sequencing of olfactory neuroblastoma (ONB) revealed somatic mutations acquired during disease progression. These findings offer insights into tumor evolution and potential drivers of metastatic ONB.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Olfactory neuroblastoma (ONB) is a rare sinonasal cancer with limited molecular understanding.
- This study aimed to characterize somatic alterations in metastatic ONB using whole genome sequencing (WGS).
Observation:
- WGS was performed on paired tumor and normal DNA from a metastatic ONB patient.
- Sixty-two somatic single nucleotide variants (SNVs) and five deletions were identified in coding regions.
Findings:
- Seven SNVs were validated; four mutations (KDR, MYC, SIN3B, NLRC4) were absent in the primary tumor but present in the metastatic lesion.
- These mutations appear to have been acquired during disease progression or post-treatment.
Implications:
- This research sheds light on the evolutionary dynamics of ONB tumor cells.
- Understanding tumor clonality and acquired mutations is crucial for comprehending ONB progression and developing targeted therapies.
