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Importance of Tumour Suppressor Genes Methylation in Sinonasal Carcinomas

Publication at First Faculty of Medicine, Faculty of Medicine in Hradec Králové |
2016

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 tumor 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 MS-MLPA (Methylation-specific Multiplex ligation-dependent probe amplification) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples.

We also compared HPV status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in genes RASSF1, CDH13, ESR1 and TP73 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 RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in those 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.