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CCNA1 promoter methylation distinguishes oral lesions

Altered DNA methylation is one of the possible factors responsible for different human diseases. The model on which we explore changes in DNA methylation in disease are potentially malignant lesions of the oral mucosa, oral lichen planus (OLP) and oral lichenoid lesions (OLL). These two lesions are difficult to distinguish clinically and histopathologically, while the therapy for them is quite different (Mravak-Stipetić et al, ScientificWorldJournal 2014). Therefore, there is a strong need to find new approach that would easily distinguish OLP from OLL. Epigenetic biomarkers, such as methylated genes could point to changes even before they can be clinically detected. Herein, we will examine the methylation status of important cell cycle regulator, CCNA1 gene (cyclin A1) in normal oral mucosa and oral precancerous lesions. We will identify CCNA1 promoter methylation in healthy subjects and in those with changes in the oral mucosa. Namely, our previous study have shown that different methylation of CCNA1 gene could be a good biomarker of mucosal diseases of the cervix (Nina Milutin Gašperov et al, PLoS ONE 2015). So, we assumed that this gene could also be changed substantially in the oral mucosa, particularly in the OLP and OLL diagnosis. Moreover, the study of Hanahan et al. (Cell 2011) showed that methylation of CCNA1 promoter was significantly associated with HPV positivity in head and neck squamous cell carcinoma (HNSCC). Hence, we will also investigate the HPV status in precancerous lesions as well as in healthy specimens. The OLP and OLL diagnoses are based on clinical examination and confirmed by histopathology. The method of methylation specific polymerase chain reaction (MSP) will be used to determine the CCNA1 gene promoter methylation status. The methylation profiles will be correlated with different diagnosis of the oral mucosa as well as the controls. Our preliminary results point out the CCNA1 promoter methylation differences between normal and probably malignant lesions of the oral mucosa.

HPV, HNSCC, oral mucosa, OLP, OLL, DNA methylation, CCNA1

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