The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.
The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.
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全球DNA甲基化替代线路1甲基化与MGMT启动子甲基化相关，是神经胶质瘤的更好预后因素。
DOI：
10.1371/journal.pone.0023332
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wakabayashi T
中科院分区：
文献类型：
--
作者：
Ohka F;Natsume A;Motomura K;Kishida Y;Kondo Y;Abe T;Nakasu Y;Namba H;Wakai K;Fukui T;Momota H;Iwami K;Kinjo S;Ito M;Fujii M;Wakabayashi T
神经胶质瘤是成人中枢神经系统中最常见的原发性脑肿瘤。尽管使用烷化剂替莫唑胺（TMZ），多形性胶质母细胞瘤（GBM，WHO 4级）具有令人沮丧的预后，并且甚至低级别胶质瘤（LGG，WHO 2级）最终转化为恶性继发性GBM。尽管GBM患者受益于O 6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子的超甲基化（这是TMZ耐药的主要决定因素），但最近的研究表明MGMT启动子甲基化对TMZ的疗效具有预后和预测意义。全基因组中的胶质瘤-CpG岛甲基化表型（G-CIMP）被证明是GBM患者生存率提高的重要预测因子。总的来说，我们假设MGMT启动子甲基化可能反映了整体DNA甲基化。此外，在LGG中，MGMT启动子甲基化的意义仍未确定。在目前的研究中，我们的目的是确定临床，遗传和表观遗传学特征（包括LINE-1和不同的癌症相关基因）与新诊断的57例LGG和54例GBM患者的临床结局之间的相关性。在这里，我们证明了（1）IDH 1/2突变与LGG中MGMT启动子甲基化和1 p/19 q共缺失密切相关，（2）原发性和继发性GBM中LINE-1甲基化水平低于LGG和正常脑组织，（3）胶质瘤中LINE-1甲基化与MGMT启动子甲基化成比例，和（4）即使与MGMT启动子甲基化相比，在原发性GBM中，较高的LINE-1甲基化是有利的预后因素。LINE-1作为一种全局性的DNA甲基化标志物，可能成为胶质瘤的一个有前途的标志物。
Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O 6-methylguanine-DNA methyltransferase (MGMT) that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.
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影响因子：
45.3
作者：
Hegi, Monika E.;Liu, Lili;Gilbert, Mark R.
通讯作者：
Gilbert, Mark R.
影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R