[Total DNA methylation profile in assessing the MGMT gene promoter status in malignant gliomas].

Q4 Medicine Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko Pub Date : 2023-01-01 DOI:10.17116/neiro20238706152

E I Petrova, S A Galstyan, E N Telysheva, M V Ryzhova

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引用次数: 0

Abstract

Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter is currently the most important prognostic biomarker in therapy of IDH-wild-type glioblastoma. One can obtain information about this methylation from total DNA methylation profile.

Objective: To analyze the DNA methylation signal intensity in the MGMT gene in samples of malignant gliomas and identify the most significant genomic positions for calculating the MGMT gene promoter status for further improvement of diagnostics and prediction of therapeutic options in patients with malignant gliomas.

Material and methods: The study is based on 43 samples (frozen tissue or paraffin blocks) from patients with malignant gliomas. Tumor DNA samples were prepared using the Illumina Infinium MethylationEPIC BeadChip Kit and the Illumina Next-Seq 550 Sequencing System platform. DNA methylation profiles were analyzed using computational algorithms in the R language, specialized libraries minfi and mgmtstp27, as well as basic statistical functions in the Rstudio environment.

Results: We established the MGMT gene promoter status in 43 samples of malignant gliomas considering total DNA methylation profile. In 24 samples (55%), the MGMT gene promoter was methylated. We compared methylation signal in certain CpG islands in groups with methylated and unmethylated MGMT gene promoters and identified the most significant positions for further improvement of data analysis algorithm.

Conclusion: These data demonstrate the possibilities and prospects for further improvement of algorithm for analysis of the MGMT gene promoter status based on total DNA methylation profile in patients with malignant gliomas as an alternative to methyl-specific PCR. Our results are consistent with data of other neuro-oncology researchers. Indeed, computational methods like MGMT-STP27 are quite powerful and can be used in scientific and clinical practice to assess prognosis and make decisions about chemotherapy with alkylating agents.

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[评估恶性胶质瘤中 MGMT 基因启动子状态的 DNA 甲基化总谱]。

O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子的甲基化是目前治疗IDH-Wild型胶质母细胞瘤最重要的预后生物标志物。人们可以从DNA甲基化总谱中获得有关该甲基化的信息：分析恶性胶质瘤样本中 MGMT 基因的 DNA 甲基化信号强度，并确定计算 MGMT 基因启动子状态的最重要的基因组位置，以进一步改进诊断和预测恶性胶质瘤患者的治疗方案：研究基于43个恶性胶质瘤患者样本（冰冻组织或石蜡块）。使用Illumina Infinium MethylationEPIC BeadChip试剂盒和Illumina Next-Seq 550测序系统平台制备肿瘤DNA样本。使用 R 语言的计算算法、专用库 minfi 和 mgmtstp27 以及 Rstudio 环境中的基本统计功能分析了 DNA 甲基化图谱：我们对 43 份恶性胶质瘤样本进行了 DNA 甲基化总谱分析，确定了 MGMT 基因启动子的状态。在 24 个样本（55%）中，MGMT 基因启动子发生了甲基化。我们比较了甲基化和未甲基化 MGMT 基因启动子组中某些 CpG 岛的甲基化信号，并确定了最重要的位置，以便进一步改进数据分析算法：这些数据表明，在恶性胶质瘤患者中，基于总 DNA 甲基化图谱分析 MGMT 基因启动子状态的算法具有进一步改进的可能性和前景，可替代甲基特异性 PCR。我们的研究结果与其他神经肿瘤学研究人员的数据一致。事实上，像MGMT-STP27这样的计算方法非常强大，可用于科学和临床实践，以评估预后并做出使用烷化剂化疗的决定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko Medicine-Neurology (clinical)

CiteScore

0.70

自引率

0.00%

发文量

期刊介绍： Scientific and practical peer-reviewed journal. This publication covers the theoretical, practical and organizational problems of modern neurosurgery, the latest advances in the treatment of various diseases of the central and peripheral nervous system. Founded in 1937. English version of the journal translates from Russian version since #1/2013.