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DNA methylation in healthy oral mucosa and head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the 6th most frequent malignancy in the world, with over 600, 000 new cases diagnosed each year. Although it is known that the main risk factors are excessive alcohol and tobacco consumption, there is a strong need to find new biomarkers of this disease. The most appropriate biomarkers would be those that would point out changes in epithelial cells before carcinoma occurence. Epigenetic biomarkers, such as methylated genes could point to changes even before they can be clinically detected. Altered DNA methylation is one of the possible factors associated with the HNSCC development. The model on which we explore changes in DNA methylation are normal oral mucosa tissue and HNSCC tissue. Our previous studies have shown that different methylation of some cellular genes could be a good biomarker of mucosal diseases of the cervix. Hence, we assumed that those genes could also be changed substantially in the oral mucosa. We already have studied methylation of those genes in oral lesions that are potentally malignant. Herein, we are examining gene methylation status in HNSCC cells in relation to normal oral mucosa oftumor suppressor genes (i.e. RARB2) and genes involved in cell cycle regulation, transcription, apoptosis, differentiation and chromosomes repair (i.e. CCNA1, C13ORF18, hTERT1, hTERT2, TWIST1). The methylation specific polymerase chain reaction (MSP) is used to determine genes promoter methylation status. The methylation profiles will be age correlated as well as with the diagnosis. Our preliminary results point out that promoter methylation of some of the investigated genes significantlly differenciate between normal oral samples and HNSCC samples.

HNSCC, HPV, oral mucosa, DNA methylation, epigenetic biomarkers

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