Promoter methylation of p16INK4, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma
Promoter methylation of p16INK4, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma
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作者：
Li, J;El-Naggar, A;Mao, L
背景启动子甲基化是多种肿瘤中抑癌基因失活的常见机制。然而，很少有人知道它在涎腺腺样囊性癌（ACC）的发展中的作用。在目前的研究中，作者调查了启动子甲基化是否在ACC中常见，以及它是否可能影响ACC的发育。基因p16（INK4a），RASSF1A，DAPK和MGMT的启动子甲基化状态，这是重要的细胞生长调节，细胞凋亡和DNA修复，确定在60例ACC患者的肿瘤标本的组织切片中使用甲基化特异性聚合酶链反应。结果：60例肿瘤中，p16（INK4a）基因启动子甲基化阳性28例（47%），RASSF1A、DAPK和MGMT基因启动子甲基化阳性分别为25例（42%）、16例（27%）和4例（7%）。46个肿瘤（77%）在4个启动子中的>= 1个中具有DNA甲基化，20个肿瘤（33%）在2个启动子中具有DNA甲基化，6个肿瘤（10%）在>= 3个启动子中具有DNA甲基化，并且1个肿瘤（2%）在所有4个启动子中具有DNA甲基化。RASSF1A启动子甲基化在高级别肿瘤中的发生率高于低级别肿瘤（P = 0.009）、晚期肿瘤（P = 0.008）和有转移的肿瘤（P = 0.005）。p16（INK4a）、RASSF1A和DAPK启动子甲基化在ACC中常见，这种甲基化可能影响ACC的发生。RASSF1A启动子甲基化在高级别肿瘤和转移性肿瘤中的高频率表明该基因在ACC的进展中发挥作用。
BACKGROUND. Promoter methylation is a common mechanism of inactivation of tumor suppressor genes in multiple tumor types. However, little is known about its role in the development of adenoid cystic carcinoma of the salivary gland (ACC). In the current study, the authors investigated whether promoter methylation is common in ACC and whether it may influence ACC development.METHODS. The promoter methylation status of the genes p16(INK4a), RASSF1A, DAPK, and MGMT, which are important in cell growth regulation, apoptosis, and DNA repair, was determined in tissue sections of tumor samples from 60 patients with ACC using methylation-specific polymerase chain reaction. The association between methylation status and patients' clinical and pathologic characteristics were assessed.RESULTS, Of the 60 tumors, DNA methylation of the p16(INK4a) promoter was detected in 28 tumors (47%); the respective values DNA methylation of the RASSF1A, DAPK, and MGMT promoters were 25 tumors (42%), 16 tumors (27%), and 4 tumors (7%), respectively. Forty-six tumors (77%) had DNA methylation in >= 1 of the 4 promoters, 20 tumors (33%) had DNA methylation in 2 promoters, 6 tumors (10%) had DNA methylation in >= 3 promoters, and 1 tumor (2%) had DNA methylation in all 4 promoters. RASSF1A promoter methylation was more frequent in high-grade tumors than in low-grade tumors (P = 0.009), in advanced-stage tumors (P = 0.008), and in tumors with metastasis (P = 0.005).CONCLUSIONS. Promoter methylation of p16(INK4a), RASSF1A, and DAPK was common in ACC, and it is possible that such methylation may influence the development of ACC. The high frequency of RASSF1A promoter methylation in high-grade tumors and in tumors with metastasis suggested a role for this gene in the progression of ACC.