颈静脉球体瘤中多种凋亡相关基因启动子甲基化状态及意义分析

Hypermethylationand clinical significance of DcR1，DcR2， DR4，DR5 promoters in jugular paragangliomas

摘要:

目的探讨颈静脉球体瘤中凋亡相关基因诱捕受体1（decoyreceptor 1,DcR1），诱捕受体2（DcR2），死亡受体4（deathreceptor 4， DR4），死亡受体5（DR5）启动子甲基化状态及其临床意义。方法采用甲基化特异性PCR（MSP）检测12例颈静脉球体瘤中四个凋亡相关基因DcR1、DcR2、DR4、DR5启动子甲基化状态。同期收集腮腺良性肿瘤手术切除的正常耳大神经组织作为对照。结果12例颈静脉球体瘤均存在甲基化，DcR1、DcR2、DR4、DR5在颈静脉球体瘤中均存在不同程度的甲基化，甲基化比率为DcR1 36.4%、DcR2 41.7%、DR4 75.0%、DR5 33.3%；正常对照中均无甲基化。且甲基化水平较高（MI＞0.50）的患者较甲基化水平低（MI≤0.05）的患者发病年龄早（P=0.0189）。结论DcR1、DcR2、DR4、DR5在颈静脉球体瘤中均存在甲基化，且与肿瘤的发生相关，甲基化水平高提示患者发病早，疾病较为严重。DNA甲基化是可逆转过程，可能成为今后靶向治疗的有效靶点。

关键词:颈静脉球体瘤|DNA甲基化|甲基化特异性PCR（MSP）

Abstract:

Abstract:ObjectiveTo analyze the methylation status of DcR1, DcR2, DR4, DR5 gene promoters in jugular paraganglioma and to study their clinical significance.MethodsMethylationspecific PCR (MSP) was used to analyze the methylation of the 4 promoters in 12 jugular paragangliomaspecimens. Great auricular nerve specimens obtained from patients suffering from benign tumor of parotid gland were chosen as control.ResultsAll the four genes showed methylation of promoters in jugular paraganglioma with respective methylation rates of 36.4%, 41.7%, 75.0% and 33.3%. Nomethylation of promoters could be detected in the normal nerves. Patients with high methylation index (MI>0.05) were younger at diagnosis than those with low methylation index(MI≤0.05，P=0.0189).ConclusionsMethylation of DcR1,DcR2,DR4 and DR5 promoters exists in jugular paragangliomas and maybe associated with the genesis and development of this tumor. Due to its reversibility, methylationis a potential targetin furthertargeted therapy of tumor.

Key words:Jugular paragangliomas| DNA methylation| Methylationspecific PCR