共 43 条
A novel analytical model of MGMT methylation pyrosequencing offers improved predictive performance in patients with gliomas
被引:38
作者:

Chai, Rui-Chao
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机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Liu, Yu-Qing
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机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Zhang, Ke-Nan
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机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
Chinese Glioma Genome Atlas, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Wu, Fan
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h-index: 0
机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Zhao, Zheng
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机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Wang, Kuan-Yu
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机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
Chinese Glioma Genome Atlas, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Jiang, Tao
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h-index: 0
机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
Chinese Glioma Genome Atlas, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China

Wang, Yong-Zhi
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h-index: 0
机构:
Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
Chinese Glioma Genome Atlas, Beijing, Peoples R China Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
机构:
[1] Capital Med Univ, Beijing Neurosurg Inst, Dept Mol Neuropathol, Beijing, Peoples R China
[2] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
[3] Chinese Glioma Genome Atlas, Beijing, Peoples R China
基金:
中国国家自然科学基金;
关键词:
GENE PROMOTER METHYLATION;
O-6-METHYLGUANINE-DNA METHYLTRANSFERASE;
CUTOFF VALUE;
CPG ISLAND;
GLIOBLASTOMA;
TEMOZOLOMIDE;
ASSAY;
SIGNATURE;
SURVIVAL;
BENEFIT;
D O I:
10.1038/s41379-018-0143-2
中图分类号:
R36 [病理学];
学科分类号:
100104 ;
摘要:
The methylation status of the promoter of MGMT gene is a crucial factor influencing clinical decision-making in patients with gliomas. MGMT pyrosequencing results are often dichotomized by a cut-off value based on an average of several tested CpGs. However, this method frequently results in a "gray zone", representing a dilemma for physicians. We therefore propose a novel analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs 75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive performances of the novel and traditional averaging models were compared in 135 patients who received temozolomide using receiver operating characteristic curves and Kaplan-Meier curves, and in patients stratified according to isocitrate dehydrogenase gene mutation status. The results were validated in an independent cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was observed in most gliomas. The optimal cut-off value for each individual CpG varied from 4-16%. The current analysis defined MGMT promoter methylation as occurring when at least three CpGs exceeded their respective cut-off values. This novel analysis could accurately predict the prognosis of patients in the methylation "gray zone" according to the standard averaging method, and improved the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in cohorts A, B, and the validation cohort, respectively, demonstrating superiority of this analytical method in all three cohorts. Furthermore, the advantages of the novel analysis were retained regardless of WHO grade and isocitrate dehydrogenase gene mutation status. In conclusion, this novel analytical model offers an improved clinical predictive performance for MGMT pyrosequencing results and is suitable for clinical use in patients with gliomas.
引用
收藏
页码:4 / 15
页数:12
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Hau, P
论文数: 0 引用数: 0
h-index: 0
机构: Univ Lausanne Hosp, Dept Neurosurg, Lab Tumor Biol & Genet, Lausanne, Switzerland

Mirimanoff, RO
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h-index: 0
机构: Univ Lausanne Hosp, Dept Neurosurg, Lab Tumor Biol & Genet, Lausanne, Switzerland

Cairncross, JG
论文数: 0 引用数: 0
h-index: 0
机构: Univ Lausanne Hosp, Dept Neurosurg, Lab Tumor Biol & Genet, Lausanne, Switzerland

Janzer, RC
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h-index: 0
机构: Univ Lausanne Hosp, Dept Neurosurg, Lab Tumor Biol & Genet, Lausanne, Switzerland

Stupp, R
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h-index: 0
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机构:
JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA

Graff, JR
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JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA

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Nelkin, BD
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机构:
JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA

Baylin, SB
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Rieger, Johannes
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机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Koch, Dorothee
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Loeser, Simon
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Blaschke, Britta
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机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Kortmann, Rolf-Dieter
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Steinbach, Joachim P.
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Hundsberger, Thomas
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Wick, Wolfgang
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Meyermann, Richard
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Tan, Ta-Chih
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Sommer, Clemens
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Bamberg, Michael
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h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Reifenberger, Guido
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany

Weller, Michael
论文数: 0 引用数: 0
h-index: 0
机构: Univ Tubingen, Dept Clin Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany