Malignant transformation-related genes in meningiomas: allelic loss on 1p36 and methylation status of p73 and RASSF1A
Malignant transformation-related genes in meningiomas: allelic loss on 1p36 and methylation status of p73 and RASSF1A
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DOI：
10.3171/jns-07/08/0398
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发表时间：
2007-08-01
影响因子：
4.1
通讯作者：
Yoshida, Jun
中科院分区：
文献类型：
--
作者：
Nakane, Yukimi;Natsume, Atsusih;Yoshida, Jun
Object.脑膜瘤的分析支持染色体臂1 p的杂合性丢失（洛）在恶性肿瘤中起重要作用的建议。本研究的目的是通过检测脑膜瘤1 p洛缺失、RASSF 1A和p73基因启动子甲基化来鉴定脑膜瘤从良性发展到非典型和间变性的相关基因。作者研究了37例脑膜瘤患者的40例手术标本（22例WHO I级、II级和7例III级）。采用微卫星标记分析1 p36位点的洛缺失，甲基化特异性聚合酶链反应分析p73和RASSF 1A基因启动子甲基化。1 p洛缺失在Ⅰ级肿瘤中未检出，而在Ⅱ级和Ⅲ级肿瘤中检出率超过80%。在II级和III级肿瘤中分别观察到81.8%和71.4%的p73启动子甲基化，但在任何I级肿瘤中均未观察到;在I级、II级和III级肿瘤中分别观察到18.2%、63.6%和42.9%的RASSF 1A启动子甲基化。有趣的是，在恶性转化的肿瘤中检测到1 p洛缺失和p73启动子高甲基化，而在低级别原发肿瘤中未检测到。基于脑膜瘤累积获得遗传改变从而从良性进展到非典型和间变性状态的假设，p73或RASSF 1A沿着甲基化状态的遗传改变以及1 p洛缺失可能导致脑膜瘤的恶性转化。这种类型的遗传指纹可能发挥诊断和治疗作用。
Object. Analysis of meningiomas supports the suggestion that loss of heterozygosity (LOH) of chromosome arm 1 p plays an important role in malignancy. The aim of this study was to identify genes related to meningioma progression from the benign state to the atypical and anaplastic states by examining 1p LOH and the promoter methylation of RASSF1A and p73.Methods. The authors studied 40 surgical specimens (22 WHO Grade I, II Grade II, and seven Grade III) obtained in 37 patients with meningioma. The LOH at 1p36 was analyzed using microsatellite markers, and promoter methylation of p73 and RASSF1A was analyzed using methylation-specific polymerase chain reaction.Results. No 1p LOH was detected in the Grade I tumors, whereas it was detected in more than 80% of the Grade II and III tumors. Methylation of the p73 promoter was observed in 81.8 and 71.4% of the Grade II and III tumors, respectively, but it was not observed in any of the Grade I tumors; methylation of the RASSF1A promoter was observed in 18.2, 63.6, and 42.9% of the Grade I, II, and III tumors, respectively. Interestingly, 1p LOH and p73 promoter hypermethylation were detected in the malignantly transformed tumors but not in the lower-grade primary ones.Conclusions. Based on the hypothesis that meningiomas cumulatively acquire genetic alterations and thus progress from the benign to the atypical and anaplastic states, genetic alterations in the methylation status of p73 or RASSF1A along with 1p LOH may result in the malignant transformation of a meningioma. This type of genetic fingerprint may play both diagnostic and therapeutic roles.