p16INK4a、RASSF1A和DAPK的启动子甲基化在涎腺腺样囊性癌中很常见。

Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma.

作者信息

Li Jiang, El-Naggar Adel, Mao Li

机构信息

College of Stomatology, Shanghai Second Medical University, Shanghai, China.

出版信息

Cancer. 2005 Aug 15;104(4):771-6. doi: 10.1002/cncr.21215.

DOI:10.1002/cncr.21215

PMID:15959912

Abstract

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 > or = 1 of the 4 promoters, 20 tumors (33%) had DNA methylation in > or = 2 promoters, 6 tumors (10%) had DNA methylation in > or = 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.

摘要

背景

启动子甲基化是多种肿瘤类型中肿瘤抑制基因失活的常见机制。然而，其在涎腺腺样囊性癌（ACC）发生发展中的作用却鲜为人知。在本研究中，作者调查了启动子甲基化在ACC中是否常见以及它是否可能影响ACC的发生发展。

方法

采用甲基化特异性聚合酶链反应，对60例ACC患者肿瘤样本的组织切片中p16(INK4a)、RASSF1A、DAPK和MGMT基因的启动子甲基化状态进行检测，这些基因在细胞生长调控、细胞凋亡和DNA修复中起重要作用。评估甲基化状态与患者临床及病理特征之间的相关性。

结果

在60个肿瘤中，28个肿瘤（47%）检测到p16(INK4a)启动子的DNA甲基化；RASSF1A、DAPK和MGMT启动子的DNA甲基化率分别为25个肿瘤（42%）、16个肿瘤（27%）和4个肿瘤（7%）。46个肿瘤（77%）在4个启动子中的≥1个存在DNA甲基化，20个肿瘤（33%）在≥2个启动子中存在DNA甲基化，6个肿瘤（10%）在≥3个启动子中存在DNA甲基化，1个肿瘤（2%）在所有4个启动子中均存在DNA甲基化。RASSF1A启动子甲基化在高级别肿瘤中比在低级别肿瘤中更常见（P = 0.009），在晚期肿瘤中更常见（P = 0.008），在有转移的肿瘤中更常见（P = 0.005）。