Global DNA methylation status in laryngeal cancer

Abstract

Laryngeal squamous cell carcinoma (LSCC) belongs to the heterogeneous group of head and neck cancers. In the etiology of LSCC, beside important environmental factors, genetic and epigenetic factors play a role in defining an individual's susceptibility to LSCC.One such epigenetic factor is DNA hypomethylation, which due to the large heterogeneity of the tissue, and invasiveness of the methods used, is often evaluated in easily available tissue, such as peripheral blood, for cancer screening.In this study we evaluated global DNA methylation status in laryngeal cancer tissues compared to normal laryngeal tissues and peripheral blood leukocytes in a homogeneous group of 72 patients with LSCC using a UPLC-based method (ultra performance liquid chromatography) to assess the total content of 5'-methylcytosine.Among the 72 patients, aged from 43 to 86 (mean 59.19, standard deviation 7.99),were 64 men and 8 women. A survey of the patients was carried out regarding their age at onset, exposure to environmental carcinogens (alcohol, cigarettes, etc.), the type of treatment, duration of treatment from the time of diagnosis and family history. Each tumor was characterized in terms of clinical and pathological features.We found DNA hypomethylation both in tumor tissue and normal tissue (about 56% and 49% of tumor and normal tissues, respectively, were substantially hypomethylated. There was a highly significant correlation between the levels of 5'-methylcytosine in these two types of tissue (p = 0.001, Spearman's test for correlation). The level of 5-methylcytosine in blood leukocytes was higher than in cancerous and normal tissues. A negative correlation was found between tumor grade and blood levels of 5-methylcytosine.The level of leukocyte DNA methylation measured using total 5-methylcytosine content cannot be used as a surrogate marker for genome methylation status in cancer tissues. Further studies are necessary to determine the correlation between the tumor grade and blood levels of 5-methylcytosine.Keywords: epigenetic, DNA hypomethylation, laryngeal cancer, head and neck cancer Abstract 2 (150 words) Background

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