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脑膜瘤中MGMT基因启动子的甲基化状态

Methylation status of MGMT gene promoter in meningiomas.

作者信息

de Robles Paula, McIntyre John, Kalra Sanjog, Roldán Gloria, Cairncross Gregory, Forsyth Peter, Magliocco Tony, Hamilton Mark, Easaw Jacob

机构信息

Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.

出版信息

Cancer Genet Cytogenet. 2008 Nov;187(1):25-7. doi: 10.1016/j.cancergencyto.2008.07.006.

Abstract

Meningiomas are usually cured by surgical resection. However, approximately 10% are characterized by more aggressive clinical behavior and higher risk of recurrence. Typically, recurrent meningiomas require further surgical resection followed, in some cases, by radiotherapy. To date, no chemotherapeutic agent has proven to be effective in either preventing or treating recurrence. The alkylating chemotherapeutic agent, Temozolomide (TMZ) has shown to increase overall survival in patients with glioblastoma (GBM) but its effectiveness for other types of brain tumor is less known. The clinical benefit of TMZ seems to be limited to those GBM tumors with promoter methylation of the MGMT gene. In this study, we assessed if a biologic rationale exists to support the use of TMZ as a treatment for meningiomas by assessing the MGMT promoter methylation status in these tumors using methylation specific PCR. We investigated the MGMT promoter methylation status in 36 tumors (32 newly diagnosed; 4 recurrent). Histologically, the majority were grade I. Patients were primarily female (64%) with a mean age of 52. None of the meningiomas in our series showed MGMT gene promoter methylation. Based on these data, we conclude that there is no biological rational to suggest that TMZ might have significant anti-meningioma activity.

摘要

脑膜瘤通常通过手术切除治愈。然而,约10%的脑膜瘤具有更具侵袭性的临床行为和更高的复发风险。通常,复发性脑膜瘤需要进一步手术切除,某些情况下还需进行放射治疗。迄今为止,尚无化疗药物被证明对预防或治疗复发有效。烷化剂化疗药物替莫唑胺(TMZ)已显示可提高胶质母细胞瘤(GBM)患者的总生存率,但其对其他类型脑肿瘤的有效性尚不清楚。TMZ的临床益处似乎仅限于那些MGMT基因启动子甲基化的GBM肿瘤。在本研究中,我们通过甲基化特异性PCR评估这些肿瘤中MGMT启动子甲基化状态,以确定是否存在生物学依据支持将TMZ用于治疗脑膜瘤。我们研究了36例肿瘤(32例新诊断;4例复发)的MGMT启动子甲基化状态。组织学上,大多数为I级。患者以女性为主(64%),平均年龄52岁。我们系列中的脑膜瘤均未显示MGMT基因启动子甲基化。基于这些数据,我们得出结论,没有生物学依据表明TMZ可能具有显著的抗脑膜瘤活性。

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