髓母细胞瘤患者血浆Ras相关区域家族1A基因甲基化的意义

摘要

目的 探讨髓母细胞瘤(MB)患者血浆逆转录病毒相关序列(RAS)家族1A(RASSF1A)基因启动子甲基化的临床意义.方法 收集82例MB患者的血浆和肿瘤标本,采用甲基化特异性聚合酶链式反应(PCR)方法,检测血浆和肿瘤组织的RASSF1A启动子甲基化状况,并分析其与临床病理特征的关系.同期收集43例幕下良性病变患者的肿瘤组织和血液标本以及19例健康体检者的血浆作为对照.结果 49份MB瘤组织中呈RASSF1A基因甲基化阳性,检出率为59.76％.40份血浆呈RASSF1A基因启动子甲基化阳性,检出率为48.78％.血浆中甲基化频率与MB组织中甲基化频率显著相关(r =0.868,P＜0.001).检测血浆中RASSF1A基因甲基化的敏感性为97.50％,特异性为76.19％,RASSF1A基因甲基化与MB分子生物学分型、临床分期相关(P＜0.01),与患者年龄、性别、肿瘤部位和病理类型无相关性(P ＞0.05).同期收集的幕下良性病变患者的肿瘤组织与血浆中、以及健康体检者的血浆中均为未检出该基因甲基化.结论 血浆中RASSF1A基因甲基化频率不仅与MB组织中的甲基化频率显著相关,还与MB分子生物学分型、临床分期具有相关性.%Objective The correlation between RAS-association domain family 1A (RASSF1 A) gene methylation in plasma and clinicopathological features of medulloblastoma was invesitigated.Methods Plasma and tumor tissue of 82 medulloblastoma patients and 43 patients with benign infratentorial tumor were included in the study,and the plasma of 19 healthy subjects was served as normal controls.The methylation status of RASSF1A gene in plasma and tumor tissue was detected by methylation-specific polymerase chain reaction (MSPCR).Results RASSF1A gene methylation rate was 59.76％ in medulloblastoma tissue and 48.78％ in paired plasma.The gene methylation in plasma was significantly correlated with that in medulloblastoma tissue (r =0.868,P ＜ 0.001).The sensitivity and specificity of RASSF1A gene methylation in plasma were 97.50％ and 76.19％,respectively.And the methylation of RASSF1A gene was correlated with the tumor molecular classification and tumor clinical stage (P ＜ 0.05),but had no correlation to gender,age,tumor location and tumor pathological type of patients (P ＞ 0.05).In addition,no RASSF1A gene methylation was found in plasma and tumor from benign infratentorial tumor patients and healthy subjects.Conclusion The methylation rate of RASSF1A gene in plasma is significantly correlated with that in medulloblastoma tissue.Additionally,the gene methylation is also correlated with the molecular classification and clinical stage of medulloblastoma.