MGMT gene promoter methylation by pyrosequencing method correlates volumetric response and neurological status in IDH wild-type glioblastomas.

MGMT gene promoter methylation by pyrosequencing method correlates volumetric response and neurological status in IDH wild-type glioblastomas.
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DOI:
10.1007/s11060-022-03999-5
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发表时间:
2022-05
影响因子:
3.9
通讯作者:
Narita, Yoshitaka
Narita, Yoshitaka
中科院分区:
医学2区
文献类型:
--
作者:
Hosoya, Tomohiro;Takahashi, Masamichi;Honda-Kitahara, Mai;Miyakita, Yasuji;Ohno, Makoto;Yanagisawa, Shunsuke;Omura, Takaki;Kawauchi, Daisuke;Tamura, Yukie;Kikuchi, Miyu;Nakano, Tomoyuki;Yoshida, Akihiko;Igaki, Hiroshi;Matsushita, Yuko;Ichimura, Koichi;Narita, Yoshitaka

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尽管O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)启动子甲基化分析在预测放化疗反应和胶质母细胞瘤患者预后方面的有用性已被广泛报道,但关于如何通过焦磷酸测序方法定义MGMT启动子甲基化百分比(MGMTpm%)截止值仍没有达成共识。本研究的目的是通过体积分析确定 MGMT 启动子甲基化状态的最佳截止值,重点关注 MRI 测量的肿瘤体积比 (TVR)。这项回顾性研究包括新诊断的 IDH 野生型胶质母细胞瘤患者,手术后有残留肿瘤,随后接受替莫唑胺局部放疗。 TVR 定义为初始放化疗后 6 个月时的肿瘤体积除以治疗开始前的肿瘤体积。使用焦磷酸测序分析 16 个 CpG 岛 (74-89) 的平均 MGMTpm%。我们统计分析了 MGMTpm%、TVR 和卡诺夫斯基表现状态变化之间的相关性。该研究包括 44 名有残留肿瘤的患者。 14 名 MGMTpm% ≥ 23.9% 的患者中,有 13 名 (92.9%) 表现出 50% 或以上的容量反应,导致生存期延长;24 名 MGMTpm% < 8.2% 的患者中,17 名 (70.8%) 在初次放化疗后出现疾病进展。 MGMTpm% 8.2% 至 < 23.9% 的 6 名患者中有 3 名 (50.0%) 疾病稳定或部分缓解。通过焦磷酸测序评估 MGMTpm% 对于预测残留肿瘤的胶质母细胞瘤患者的体积反应和预后很重要。
Although the usefulness of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation analysis for predicting response to chemoradiotherapy and the prognosis of patients with glioblastoma has been widely reported, there is still no consensus regarding how to define MGMT promoter methylation percentage (MGMTpm%) cutoffs by pyrosequencing method. The aim of this study was to determine the optimal cutoff value of MGMT promoter methylation status using volumetric analysis focused on the tumor volume ratio (TVR) measured by MRI. This retrospective study included newly diagnosed IDH wild-type glioblastoma patients with residual tumor after surgery, followed by local radiotherapy with temozolomide. TVR was defined as the tumor volume at 6 months after the initial chemoradiotherapy administration divided by the tumor volume before the start of therapy. The mean MGMTpm% of 16 CpG islands (74–89) was analyzed using pyrosequencing. We statistically analyzed the correlation between MGMTpm%, TVR, and change in Karnofsky performance status. The study included 44 patients with residual tumors. Thirteen (92.9%) of 14 patients with MGMTpm% ≥ 23.9% showed 50% or more volumetric response, leading to prolonged survival, and 17 (70.8%) of 24 patients with MGMTpm% < 8.2% had progressive disease after initial chemoradiotherapy administration. Three (50.0%) of six patients with MGMTpm% 8.2% to < 23.9% had stable disease or partial response. Evaluation of MGMTpm% by pyrosequencing is important in predicting the volumetric response and prognosis of glioblastoma patients with residual tumors.
DOI: 10.1056/nejmoa043330
发表时间: 2005-03-10
影响因子: 158.5
作者:
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通讯作者: Ryan, G
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发表时间: 2015-01-01
影响因子: 3.3
作者:
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发表时间: 2007-07-01
影响因子: 4.1
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DOI: 10.1056/nejmoa043331
发表时间: 2005-03-10
影响因子: 158.5
作者:
Hegi, ME;Diserens, A;Stupp, R
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