title: Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas.
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.
authors: Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: M
authors: M
authors: Chmelařová
authors: Department of Oncology and Radiotherapy, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: I
authors: I
authors: Sirák
authors: Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: M
authors: M
authors: Mžik
authors: The Fingerland Department of Pathology, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: K
authors: K
authors: Sieglová
authors: The Fingerland Department of Pathology, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: H
authors: H
authors: Vošmiková
authors: Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors: P
authors: P
authors: Dundr
authors: Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors: K
authors: K
authors: Němejcová
authors: Department of Clinical and Molecular Pathology, Palacký University Olomouc, Faculty of Medicine and Dentistry and University Hospital Olomouc, Czech Republic.
authors: J
authors: J
authors: Michálek
authors: Department of Oncology and Radiotherapy, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: M
authors: M
authors: Vošmik
authors: Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: V
authors: V
authors: Palička
authors: The Fingerland Department of Pathology, Charles University in Prague - Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Czech Republic.
authors: J
authors: J
authors: Laco
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology* / Q000821:virology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004789:Enzyme Activation; D057890:Epigenomics; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D015820:Cadherins; C099972:H-cadherin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases