Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas

Chmelařová, Marcela; Sirák, I.; Mžik, M.; Sieglová, K.; Vošmiková, H.; Dundr, P.; Němejcová, K.; Michálek, J.; Vošmik, M.; Palička, V.; Laco, J.

doi:10.14712/fb2016062030110

Folia Biologica > Archive > 2016, Vol. 62 > Issue 3 > Importance of Tumour Suppressor Gene…

Fol. Biol. 2016, 62, 110-119

https://doi.org/10.14712/fb2016062030110

Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas

Marcela Chmelařová¹, I. Sirák², M. Mžik¹, K. Sieglová³, H. Vošmiková³, P. Dundr⁴, K. Němejcová⁴, J. Michálek⁵, M. Vošmik⁶, V. Palička¹, J. Laco³

¹Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague – Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic
²Department of Oncology and Radiotherapy, Charles University in Prague – Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic
³The Fingerland Department of Pathology, Charles University in Prague – Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic
⁴Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic
⁵Department of Clinical and Molecular Pathology, Palacký University Olomouc, Faculty of Medicine and Dentistry and University Hospital Olomouc, Czech Republic
⁶Department of Oncology and Radiotherapy, Charles University in Prague – Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic 3

Received October 2015
Accepted March 2016

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, ESR1, 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.

Keywords

MS-MLPA, DNA methylation, sinonasal carcinoma, epigenetics, HPV.

Funding

This study was supported by the Ministry of Health of the Czech Republic – conceptual development of research organization MH CZ – DRO (FNHK) 00179906, by the Charles University Research Development Schemes, Czech Republic PRVOUK P37/11 and P27/LF1/1, and by the project of the Ministry of Health of the Czech Republic – conceptual development of research organization Biobanking and Biomolecular Resources Research Infrastructure BBMRI LM2010004.