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Published on: February 28, 2019
Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas
M Chmelařová1, I Sirák2, M Mžik1
1Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
Abstract:
Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples. We also compared the human papilloma virus (HPV) status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in RASSF1, CDH13, ESR1 and TP73 genes in the sinonasal cancer group compared with the control group. HPV positivity was found in 15/64 (23.4 %) of all samples in the carcinoma group and in no sample in the control group. No correlation was found between DNA methylation and HPV status. In conclusion, our study showed that there are significant differences in promoter methylation in the RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in these genes in carcinogenesis of the sinonasal area. These findings could be used as prognostic factors and may have implications for future individualised therapies based on epigenetic changes.
Insights
Epigenetic changes, specifically promoter hypermethylation of RASSF1, CDH13, ESR1, and TP73 genes, are significantly higher in sinonasal carcinoma compared to normal tissue. These DNA methylation differences may serve as prognostic factors for sinonasal cancers.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Epigenetic alterations, particularly promoter hypermethylation, are crucial in cancer development.
- This mechanism can lead to the inactivation of critical genes like tumor suppressors and DNA repair genes.
- Sinonasal carcinoma (SNC) is a rare malignancy where the role of epigenetic changes is not fully understood.
Purpose of the Study:
- To investigate promoter methylation patterns of specific genes in SNC.
- To compare methylation status between SNC tissues and normal sinonasal tissues.
- To explore potential correlations between DNA methylation and human papillomavirus (HPV) status in SNC.
Main Methods:
- Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was employed.
- The study analyzed 64 SNC tissue samples and 19 control samples.
- HPV status was assessed and compared with DNA methylation data.
Main Results:
- Significantly higher promoter methylation was observed in RASSF1, CDH13, ESR1, and TP73 genes in SNC samples compared to controls (20% cut-off).
- HPV was detected in 23.4% of SNC cases but not in controls.
- No significant correlation was found between DNA methylation status and HPV positivity.
Conclusions:
- Distinct promoter methylation profiles exist for RASSF1, ESR1, TP73, and CDH13 genes in SNC versus normal tissue.
- These epigenetic alterations highlight their importance in SNC carcinogenesis.
- The findings suggest potential utility of these methylated genes as prognostic biomarkers and for targeted epigenetic therapies in SNC.
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