Aberrant gene promoter methylation of E-cadherin, p16INK4a, p14ARF, and MGMT in Epstein-Barr virus-associated oral squamous cell carcinomas

被引:10
作者
Burassakarn, Ati [1 ,6 ]
Pientong, Chamsai [1 ,6 ]
Sunthamala, Nuchsupha [2 ,6 ]
Chuerduangphui, Jureeporn [1 ,6 ]
Vatanasapt, Patravoot [3 ,6 ]
Patarapadungkit, Natcha [4 ,6 ]
Kongyingyoes, Bunkerd [5 ]
Ekalaksananan, Tipaya [1 ,6 ]
机构
[1] Khon Kaen Univ, Dept Microbiol, Fac Med, Khon Kaen, Thailand
[2] Mahasarakham Univ, Dept Microbiol, Fac Sci, Maha Sarakham, Thailand
[3] Khon Kaen Univ, Fac Med, Dept Otorhinolaryngol, Khon Kaen, Thailand
[4] Khon Kaen Univ, Dept Pathol, Fac Med, Khon Kaen, Thailand
[5] Khon Kaen Univ, Dept Pharmacol, Fac Med, Khon Kaen, Thailand
[6] Khon Kaen Univ, HPV & EBV & Carcinogenesis Res Grp, Khon Kaen, Thailand
关键词
Epstein-Barr virus; Promoter methylation; Oral squamous cell carcinoma; Epigenetic changes; HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; CLINICAL-IMPLICATIONS; DNA METHYLATION; DOWN-REGULATION; HUMAN CANCERS; NECK-CANCER; HYPERMETHYLATION; HEAD; EXPRESSION;
D O I
10.1007/s12032-017-0983-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The etiology of oral carcinogenesis appears to be multifactorial. There is emerging evidence of the presence of Epstein-Barr virus (EBV) in epithelial oral squamous cell carcinoma (OSCC), but an association of EBV with oral carcinogenesis has not yet been established. Although epigenetic alterations, such as aberrant DNA methylation, are known to contribute to the pathogenesis of oral cancer, the relationship of such alterations with EBV infection is little known. This study aimed to investigate the association between EBV infection and promoter methylation patterns of tumor-associated genes in OSCC tissues. A total of 165 of formalin-fixed paraffin-embedded OSCC tissues were studied (68 of EBV positive and 97 of EBV negative). The promoter methylation patterns were investigated for four tumor-associated genes, E-cadherin, p16(INK4a), p14(ARF), and MGMT, by using methylation-specific polymerase chain reaction (MSP). The frequencies of gene promoter hypermethylation in all cases were 47.3% for E-cadherin, 92.7% for p16(INK4a), 74.5% for p14(ARF), and 35.8% for MGMT. Interestingly, most of the analyzed gene promoters were more frequently hypermethylated in EBV-positive than EBV-negative cases, in particular the Ecadherin (56/22) and MGMT (38/21) gene promoters (p < 0.05). Concomitantly, hypermethylation of multiple gene promoters (>= 3) was encountered more frequently in EBV-positive samples. Hypermethylation of the E-cadherin promoter associated with EBV was more frequently observed in moderately and poorly differentiated OSCC tissues. These results indicate that epigenetic changes frequently occur in OSCCs and may partly be induced by EBV infection, therefore, EBV may involve in development and progression of the OSCCs.
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页数:9
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