胶质瘤中RASSF1A基因的高甲基化

Hypermethylation of the RASSF1A gene in gliomas.

作者信息

Gao Yunxia, Guan Ming, Su Bing, Liu Weiwei, Xu Min, Lu Yuan

机构信息

Center of Laboratory Medicine, Huashan Hospital, Fudan University, 12 Central Urumqi Road, 200040 Shanghai, P.R. China.

出版信息

Clin Chim Acta. 2004 Nov;349(1-2):173-9. doi: 10.1016/j.cccn.2004.07.006.

DOI:10.1016/j.cccn.2004.07.006

PMID:15469871

Abstract

BACKGROUND

Promoter methylation is an important pathway in transcriptional silencing of tumor suppressor genes (TSGs) in brain tumors. The identified 3p21.3 tumor suppressor gene RAS association domain family protein 1A (RASSF1A) is highly methylated in primary lung, breast and other tumors. We investigated the promoter methylation and gene expression of RASSF1A in gliomas.

METHODS

The methylation status of the promoter region of RASSF1A, p16INK4A and death-associated protein kinase (DAPK) genes was analyzed by methylation-specific PCR (MSP) in 41 surgically resected gliomas. RASSF1A expression was also detected by reverse-transcription polymerase chain reaction (RT-PCR) in 28 glioma tissues.

RESULTS

The frequencies of RASSF1A, p16INK4A and DAPK promoter methylation were 13/41 (31.7%), 3/41 (7.3%) and 6/41 (14.6%) respectively. However, the methylations of those genes were not correlated with the clinical characteristics of patients (tumor grade, tumor types and sex). Among 28 glioma tissues, 6 showed the loss of the gene (21.4%). Promoter hypermethylation of RASSF1A is associated with loss of gene expression in glioma tissues. (p=0.022).

CONCLUSIONS

Our results suggested that the RASSF1A gene might play an important role in glioma carcinogenesis. It also gives us an insight for future glioma medical therapy with a demethylating agent.

摘要

背景

启动子甲基化是脑肿瘤中肿瘤抑制基因（TSGs）转录沉默的重要途径。已确定的位于3p21.3的肿瘤抑制基因RAS关联结构域家族蛋白1A（RASSF1A）在原发性肺癌、乳腺癌和其他肿瘤中高度甲基化。我们研究了RASSF1A在胶质瘤中的启动子甲基化和基因表达情况。

方法

采用甲基化特异性PCR（MSP）分析41例手术切除的胶质瘤中RASSF1A、p16INK4A和死亡相关蛋白激酶（DAPK）基因启动子区域的甲基化状态。还通过逆转录聚合酶链反应（RT-PCR）检测了28例胶质瘤组织中RASSF1A的表达。

结果

RASSF1A、p16INK4A和DAPK启动子甲基化频率分别为13/41（31.7%）、3/41（7.3%）和6/41（14.6%）。然而，这些基因的甲基化与患者的临床特征（肿瘤分级、肿瘤类型和性别）无关。在28例胶质瘤组织中，6例显示该基因缺失（21.4%）。RASSF1A启动子高甲基化与胶质瘤组织中基因表达缺失相关（p = 0.022）。