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Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
Genomic profiling and immune landscape of olfactory neuroblastoma in China
Yunyun Yang1,2, Zhiyi Wan3, Enli Zhang3
1Department of Pathology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China.
Background:
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.
Methods:
Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.
Results:
Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.
Conclusion:
This study presents data on the genomic and immune landscape of ONB cases in China. CTNNB1 and ZNRF3 were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.
Implications For Practice:
In this study, the most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.
Insights
This study reveals key genomic alterations in olfactory neuroblastoma (ONB), identifying CTNNB1 and ZNRF3 as frequently mutated genes. Results suggest ONB may not respond well to immunotherapy, but M1 macrophages could be linked to better prognosis.
Area of Science:
- Genomics
- Oncology
- Immunology
Background:
- Olfactory neuroblastoma (ONB) is a rare cancer with limited genomic data hindering personalized treatment.
- Investigating the genomic and immune profiles of ONB in Chinese patients is crucial for understanding disease mechanisms.
Purpose of the Study:
- To analyze the genomic landscape of olfactory neuroblastoma (ONB) in Chinese patients.
- To investigate the immune microenvironment of ONB and its correlation with clinicopathological features.
Main Methods:
- Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) were performed on 19 Chinese ONB patient samples.
- Patients were stratified into low- and high-grade groups for comparative analysis.
Main Results:
- CTNNB1 and ZNRF3 were the most frequently altered genes in ONB.
- Low tumor mutation burden (TMB), PD-L1 expression, and CD8+ tumor-infiltrating lymphocytes (TILs) suggest potential immunotherapy resistance.
- Low-grade ONB exhibited significantly higher levels of CD68+ macrophages, particularly CD68+CD163- (M1-like) macrophages.
Conclusions:
- This study provides comprehensive genomic and immune data for Chinese ONB cases.
- CTNNB1 and ZNRF3 alterations are prevalent in ONB.
- ONB's low TMB, PD-L1, and CD8+ TILs indicate limited response to current immunotherapies, while M1 macrophages may be a positive prognostic factor.
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