{"title":"摘要:人胶质母细胞瘤Notch信号通路基因表达及DNA甲基化谱分析","authors":"Madhuri G. S. Aithal, R. Narayanappa","doi":"10.1158/1538-7755.CARISK16-A10","DOIUrl":null,"url":null,"abstract":"In cancer, DNA methylation affects important signal transduction pathways leading to altered receptor function, disruption of normal cell-cell interaction, etc. Since methylation occurs at a very early stage, hypermethylated promoters hold great promise as biomarkers for early detection and an effective drug target for gene reactivation. The Notch signaling pathway is one such developmental pathway governing cell fate decisions. Dysregulated Notch signaling is found to have a prominent role in the development of various cancers. Glioblastoma is the most common primary brain tumor with a very poor prognosis. Therefore it is important to study genetic and epigenetic events leading to gliomagenesis and to guide new treatment strategies. The aim of this study was to detect Notch pathway genes potentially regulated by promoter methylation in human glioblastoma. We used real-time PCR and methylation-specific PCR to study gene expression and methylation status of seven Notch pathway genes (Notch1, Notch2, Notch3, Notch4, JAG1, JAG2 and DLL3) from human glioblastoma formalin fixed paraffin embedded sections. We identified Notch3 and JAG2 promoters as methylated and Notch4 with both methylated and unmethylated promoter. Despite methylation, Notch3 gene showed robust gene expression suggesting its partial dependency on promoter methylation and the presence of alternative regulatory mechanisms. However, low gene expression of JAG2 and the absence of Notch4 gene expression suggest a possibility of epigenetic silencing. This study for the first time provides gene expression and DNA methylation profiles of Notch pathway genes from glioblastoma patient samples. We have identified genes whose expression may be regulated by epigenetic mechanisms and thus can be used as markers that may guide treatment decisions. Note: This abstract was not presented at the conference. Citation Format: Madhuri G S Aithal, Rajeswari Narayanappa. Analysis of gene expression and DNA methylation profiles of Notch signaling pathway genes in human glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. 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We used real-time PCR and methylation-specific PCR to study gene expression and methylation status of seven Notch pathway genes (Notch1, Notch2, Notch3, Notch4, JAG1, JAG2 and DLL3) from human glioblastoma formalin fixed paraffin embedded sections. We identified Notch3 and JAG2 promoters as methylated and Notch4 with both methylated and unmethylated promoter. Despite methylation, Notch3 gene showed robust gene expression suggesting its partial dependency on promoter methylation and the presence of alternative regulatory mechanisms. However, low gene expression of JAG2 and the absence of Notch4 gene expression suggest a possibility of epigenetic silencing. This study for the first time provides gene expression and DNA methylation profiles of Notch pathway genes from glioblastoma patient samples. We have identified genes whose expression may be regulated by epigenetic mechanisms and thus can be used as markers that may guide treatment decisions. Note: This abstract was not presented at the conference. Citation Format: Madhuri G S Aithal, Rajeswari Narayanappa. Analysis of gene expression and DNA methylation profiles of Notch signaling pathway genes in human glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. 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引用次数: 0
摘要
在癌症中,DNA甲基化影响重要的信号转导通路,导致受体功能改变,破坏正常的细胞-细胞相互作用等。由于甲基化发生在非常早期的阶段,超甲基化启动子作为早期检测的生物标志物和基因再激活的有效药物靶点具有很大的前景。Notch信号通路是控制细胞命运决定的发育途径之一。失调的Notch信号被发现在各种癌症的发展中具有突出的作用。胶质母细胞瘤是最常见的原发性脑肿瘤,预后很差。因此,研究导致胶质瘤形成的遗传和表观遗传事件并指导新的治疗策略具有重要意义。本研究的目的是检测人类胶质母细胞瘤中可能受启动子甲基化调控的Notch通路基因。我们采用实时荧光定量PCR和甲基化特异性PCR技术研究了人胶质母细胞瘤福尔马林固定石蜡包埋切片中7个Notch通路基因(Notch1、Notch2、Notch3、Notch4、JAG1、JAG2和DLL3)的基因表达和甲基化状态。我们发现Notch3和JAG2启动子是甲基化的,Notch4启动子是甲基化的和未甲基化的。尽管甲基化,Notch3基因仍显示出强劲的基因表达,表明其部分依赖于启动子甲基化,并存在其他调控机制。然而,JAG2基因的低表达和Notch4基因的缺失提示了表观遗传沉默的可能性。本研究首次提供了胶质母细胞瘤患者样本中Notch通路基因的基因表达和DNA甲基化谱。我们已经确定了表达可能受表观遗传机制调节的基因,因此可以用作指导治疗决策的标记。注:本摘要未在会议上发表。引文格式:Madhuri G S Aithal, Rajeswari Narayanappa。人胶质母细胞瘤Notch信号通路基因表达及DNA甲基化谱分析。[摘要]。摘自:AACR特别会议论文集:改进癌症风险预测以预防和早期发现;2016年11月16日至19日;费城(PA): AACR;Cancer epidemiology Biomarkers pre2017;26(5增刊):摘要nr - A10。
Abstract A10: Analysis of gene expression and DNA methylation profiles of Notch signaling pathway genes in human glioblastoma
In cancer, DNA methylation affects important signal transduction pathways leading to altered receptor function, disruption of normal cell-cell interaction, etc. Since methylation occurs at a very early stage, hypermethylated promoters hold great promise as biomarkers for early detection and an effective drug target for gene reactivation. The Notch signaling pathway is one such developmental pathway governing cell fate decisions. Dysregulated Notch signaling is found to have a prominent role in the development of various cancers. Glioblastoma is the most common primary brain tumor with a very poor prognosis. Therefore it is important to study genetic and epigenetic events leading to gliomagenesis and to guide new treatment strategies. The aim of this study was to detect Notch pathway genes potentially regulated by promoter methylation in human glioblastoma. We used real-time PCR and methylation-specific PCR to study gene expression and methylation status of seven Notch pathway genes (Notch1, Notch2, Notch3, Notch4, JAG1, JAG2 and DLL3) from human glioblastoma formalin fixed paraffin embedded sections. We identified Notch3 and JAG2 promoters as methylated and Notch4 with both methylated and unmethylated promoter. Despite methylation, Notch3 gene showed robust gene expression suggesting its partial dependency on promoter methylation and the presence of alternative regulatory mechanisms. However, low gene expression of JAG2 and the absence of Notch4 gene expression suggest a possibility of epigenetic silencing. This study for the first time provides gene expression and DNA methylation profiles of Notch pathway genes from glioblastoma patient samples. We have identified genes whose expression may be regulated by epigenetic mechanisms and thus can be used as markers that may guide treatment decisions. Note: This abstract was not presented at the conference. Citation Format: Madhuri G S Aithal, Rajeswari Narayanappa. Analysis of gene expression and DNA methylation profiles of Notch signaling pathway genes in human glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A10.