Quantitative analysis of MGMT promoter methylation status changes by pyrosequencing in recurrent glioblastoma.

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2023-08-01 DOI:10.1111/neup.12887
Víctor González Jiménez, Marta Brell Doval, Cristina Gómez Bellvert, Victor Goliney Goliney, Osman Salazar Asencio, Adriana Gómez Martín, Javier Ibáñez Domínguez
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引用次数: 1

Abstract

MGMT promoter methylation status can change in response to several factors, treatment with alkylating therapy being the mechanism more commonly cited in the literature. Some authors have attempted to quantify these alterations, with inconsistent results. This study aims to determine changes in MGMT promoter methylation status by pyrosequencing, which quantitatively yields results, in a cohort of patients reoperated for recurrent glioblastoma and having previously completed the Stupp protocol. Methylation status of the MGMT promoter gene of a total of 24 pairs of glioblastoma preselected tumor samples was retrospectively analyzed using pyrosequencing and depicted as percentages or categories (hypermethylated, intermediate methylation, unmethylated). Matched samples were compared using Wilcoxon signed-rank test, and log-rank test was used to establish a correlation with survival data. The median value of MGMT promoter methylation status declined after adjuvant treatment from 20.35% to 14.25% (p = 0.346). A significant correlation between methylation in primary samples and overall survival (p = 0.05) and progression-free survival (p = 0.024) was found. Intermediate methylation status at recurrence was linked to greater survival after progression, without reaching statistical significance (post-progression survival [PPS]) (p = 0.217). Although treatment with alkylating chemotherapy was a common feature in all patients of our cohort, switching in both directions was observed when MGMT promoter methylation status was analyzed as a continuous variable. These data suggest that the dynamics of epigenetics may be very complex and not entirely explained by clonal selection influenced by temozolomide.

用焦磷酸测序法定量分析复发性胶质母细胞瘤中MGMT启动子甲基化状态的变化。
MGMT启动子甲基化状态可因多种因素而改变,文献中更常引用的机制是烷基化治疗。一些作者试图量化这些变化,但结果不一致。本研究旨在通过磷酸氢测序确定MGMT启动子甲基化状态的变化,定量地得出结果,在一组复发性胶质母细胞瘤再手术患者中,之前完成了Stupp方案。使用焦磷酸测序方法回顾性分析了共24对胶质母细胞瘤预选肿瘤样本的MGMT启动子基因的甲基化状态,并描述为百分比或类别(高甲基化,中度甲基化,未甲基化)。配对样本比较采用Wilcoxon符号秩检验,并采用log-rank检验与生存数据建立相关性。辅助治疗后MGMT启动子甲基化状态中位数从20.35%下降到14.25% (p = 0.346)。初步样本的甲基化与总生存期(p = 0.05)和无进展生存期(p = 0.024)之间存在显著相关性。复发时的中间甲基化状态与进展后的更高生存率相关,但没有达到统计学意义(进展后生存率[PPS]) (p = 0.217)。虽然烷基化化疗是我们队列中所有患者的共同特征,但当将MGMT启动子甲基化状态作为一个连续变量进行分析时,可以观察到这两个方向的转换。这些数据表明,表观遗传学的动力学可能是非常复杂的,并不能完全解释由替莫唑胺影响克隆选择。
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
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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