头颈部鳞状细胞癌中肿瘤相关基因的甲基化

S. V. Kurevlev, L. Tskhovrebova, A. Aghajanyan, T. Fatkhudinov, K. Gordon, M. Azova
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摘要

介绍。头颈部肿瘤是一种异质性的恶性肿瘤,其病因不同,分子机制研究尚不充分。头颈部鳞状细胞癌患者肿瘤相关基因(RASSF1A、RASSF2、RASSF5、CDO1、MEST和WIF1) DNA甲基化状态的研究材料和方法。采用亚硫酸氢盐转化和甲基化敏感高分辨率熔解法分析了25例(男21例,女4例)颈部鳞状细胞癌患者正常组织和肿瘤组织的DNA甲基化水平。在所有组和亚组患者(喉癌和其他癌症、鳞状细胞癌角化和非角化、原发性和复发性肿瘤、吸烟者和非吸烟者)中,肿瘤组织中CDO1和WIF1基因的DNA甲基化水平与正常组织存在显著差异。肿瘤组织中CDO1基因甲基化水平在T4期和T3期亚组较t2期显著升高。CDO1和WIF1基因甲基化水平的升高及其表达的变化是参与颈部鳞状细胞癌发展的分子机制之一。它们可以被认为是这种病理的预后和诊断标记。
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Methylation of the tumor associated genes in head and neck squamous cell carcinoma
Introduction. Head and neck cancer is a heterogenous group of malignant tumors of different etiologies, molecular mechanisms of which are still insufficiently studied.Aim. Investigation of DNA methylation status of some tumor associated genes (RASSF1A, RASSF2, RASSF5, CDO1, MEST and WIF1) in patients with head and neck squamous cell carcinoma.Materials and methods. The DNA methylation level of normal and tumor tissues was analyzed using bisulfite conversion and methylation-sensitive high-resolution melting in 25 patients (21 men and 4 women) diagnosed with neck squamous cell carcinoma.Results. There were significant differences in levels of DNA methylation between tumor and normal tissues in the CDO1 and WIF1 genes in all groups and subgroups of patients (larynx and other cancers, squamous cell carcinoma keratinizing and non-keratinizing, primary and recurrent tumor, smokers and non-smokers). The methylation level in the CDO1 gene in tumor tissue was significantly increased in the T4 and T3 stage subgroups compared to T2.Conclusion. The increased level of methylation of the CDO1 and WIF1 genes, as well as changes in their expression are among the molecular mechanisms involved in the neck squamous cell carcinoma development. They can be considered as prognostic and diagnostic markers for this pathology.
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