成人胶质母细胞瘤中 IDH1 突变和 MGMT 甲基化对临床的影响

IF 1.2 Q4 GENETICS & HEREDITY Egyptian Journal of Medical Human Genetics Pub Date : 2024-03-28 DOI:10.1186/s43042-024-00516-3
Magda Sayed Mahmoud, Mohamed K. Khalifa, Amira M. Nageeb, Lobna R. Ezz El-Arab, Manal El-Mahdy, Amal Ramadan, Maha Hashim, Noha M. Bakr, Menha Swellam
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引用次数: 0

摘要

异柠檬酸脱氢酶1(IDH1)和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)在胶质母细胞瘤(GBM)中的影响因其对多种癌症预后预测的影响而备受关注。本研究旨在探讨 IDH1 突变和 MGMT 甲基化模式在 GBM 患者与非神经肿瘤疾病(NND)患者中的临床作用及其对生存标准的影响。研究人员收集了58例GBM患者和20例非神经肿瘤疾病患者的福尔马林固定石蜡包埋(FFPE)组织切片,并分别使用Cast-PCR技术和Methyl II定量PCR方法检测了IDH1突变和MGMT甲基化。结果与其他临床病理学标准和生存模式进行了评估。在15例GBM病例(15/58)中检测到了IDH1基因突变,而在NND病例中未见报道(P = 0.011)。绘制了接收者操作特征(ROC)曲线,以区分研究组间的 MGMT 甲基化情况。MGMT甲基化≥66%的患者被报告为高甲基化,在GBM病例和NND病例中分别有51.7%和100%的患者有明显记录。两者与患者的表现状态有明显差异,而 MGMT 甲基化与肿瘤大小和肿瘤位置有明显相关性。IDH1突变和MGMT甲基化与GB患者对治疗的完全反应有关。与 IDH1 野生型或 MGMT 中低度甲基化相比,IDH1 突变和 MGMT 高度甲基化的患者生存率更高,而且两者联合检测比单独检测更有利。在GB患者中检测IDH1突变和MGMT甲基化有助于预测他们对治疗的反应及其生存模式,两者联合检测比单独检测任何一种都更好。
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Clinical impact of IDH1 mutations and MGMT methylation in adult glioblastoma
Impact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma (GBM) have been of great interest due to their implications in prediction of prognosis of several types of cancer. It was aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GBM patients versus non-neuro-oncological diseases (NND) patients and their impact on survival criteria. Formalin-fixed paraffin-embedded (FFPE) tissue sections of 58 GBM and 20 non-neuro-oncological diseases patients were recruited and IDH1 mutation and MGMT methylation was detected using Cast-PCR technology and Methyl II quantitative PCR approach, respectively. Results were assessed with other clinicopathological criteria and survival patterns. IDH1 mutation was detected among 15 GBM cases (15/58) and it was not reported among NND (P = 0.011). Receiver operating characteristic (ROC) curve was plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation ≥ 66% were reported as high methylation, which was recorded significantly in 51.7% and 100% of GBM cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GB patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low–moderate methylation, respectively, and favorable survival was detected when both were combined than using either of them alone. Detection of IDH1 mutation and MGMT methylation among GB patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.
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来源期刊
Egyptian Journal of Medical Human Genetics
Egyptian Journal of Medical Human Genetics Medicine-Genetics (clinical)
CiteScore
2.20
自引率
7.70%
发文量
150
审稿时长
18 weeks
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