Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: A prospective GICNO study
Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: A prospective GICNO study
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DOI：
10.1200/jco.2006.06.3891
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发表时间：
2006-10-10
影响因子：
45.3
通讯作者：
Ermani, Mario
中科院分区：
文献类型：
--
作者：
Brandes, Alba A.;Tosoni, Alicia;Ermani, Mario
研究目的：目前尚无关于原发性间变性少突胶质细胞瘤（AO）和间变性少突星形细胞瘤（AOA）术后复发患者1 p/19 q缺失与替莫唑胺（TMZ）疗效之间关系的数据。本研究的目的是评估1 p/19 q缺失，O 6-甲基鸟嘌呤DNA甲基转移酶（MGMT）启动子甲基化，并响应率TMZ在此setting.Patients和MethodsFrom 2000年6月至2005年2月，67例患者入组; 39例（58%）有AO和28例（42%）有AOA之间的相关性。所有患者均接受TMZ 150至200 mg/m2，每28天一次。染色体1 p和19 q缺失检测荧光原位杂交和MGMT启动子甲基化分析甲基化特异性polymerase chain reaction. ResultsTotal response rate为46.3%（17个完全响应和14个部分响应）。AO患者的缓解率高于AOA患者（61.5% vs25%，P = 0.003）。在54名可评估的患者中，32名患者（47.8%）发现了1 p/19 q等位基因丢失，而37名患者（68.5%）发生了MGMT甲基化。1 p/19 q缺失与缓解率（P = 0.04）、进展时间（P = 0.003）和总生存期（P = 0.0001）显著相关。尽管MGMT启动子甲基化和1 p/19 q缺失之间存在显著一致性（P =.02），但MGMT启动子甲基化仅与总生存率呈边缘相关性（P =.09）。在这种情况下，1 p/19 q等位基因丢失是一个重要的预测和预后因素。对MGMT启动子甲基化的进一步研究应在随机试验中进行，以测试其与生存的相关性。
PurposeTo date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting.Patients and MethodsFrom June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m(2) of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction.ResultsThe overall response rate was 46.3% ( 17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P =.003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate ( P =.04), time-to-progression ( P =.003), and overall survival ( P =.0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions ( P =.02), MGMT promoter methylation showed only a borderline correlation with overall survival ( P =.09).ConclusionTMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.