DNA methylation in the malignant transformation of meningiomas.
DNA methylation in the malignant transformation of meningiomas.
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DOI：
10.1371/journal.pone.0054114
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Gao F;Shi L;Russin J;Zeng L;Chang X;He S;Chen TC;Giannotta SL;Weisenberger DJ;Zada G;Mack WJ;Wang K
脑膜瘤是中枢神经系统肿瘤，起源于大脑和脊髓的脑膜覆盖物。大多数脑膜瘤在病理上是良性或非典型的，但3-5%显示恶性特征。尽管之前对良性和非典型脑膜瘤进行了研究，但参与恶变的关键分子途径仍有待确定，恶性脑膜瘤的表观遗传学改变程度也是如此。在这项研究中，我们探讨了10个良性，5个非典型和4个恶性脑膜瘤的DNA甲基化的景观。与良性肿瘤相比，非典型和恶性脑膜瘤表现出更高的整体DNA低甲基化。聚类分析很容易将恶性肿瘤与非典型和良性肿瘤分开，这意味着DNA甲基化模式可以作为恶性肿瘤的诊断生物标志物。在恶性脑膜瘤中具有高甲基化CpG岛的基因（如HOXA 6和HOXA 9）在早期发育阶段倾向于与多梳抑制复合物（PRC）的结合位点相一致。在恶性和良性脑膜瘤中，大多数在启动子处具有高甲基化CpG岛的基因被抑制，这表明在恶性脑膜瘤中基因沉默机制从PRC结合到DNA甲基化的切换。一个例外是MAL 2基因，其在良性组中高表达而在恶性组中沉默，代表DNA甲基化诱导的从头基因沉默。总之，我们的研究结果表明，恶性脑膜瘤有不同的DNA甲基化模式相比，其良性和非典型的同行，差异甲基化的基因可能作为诊断生物标志物或恶性转化的候选致病基因。
Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3–5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation.
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影响因子：
11.2
作者：
Jair, KW;Bachman, KE;Schuebel, KE
通讯作者：
Schuebel, KE
影响因子：
3.5
作者：
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通讯作者：
LINDSAY, H
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作者：
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影响因子：
3.5
作者：
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通讯作者：
Bestor, TH
影响因子：
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作者：
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通讯作者：
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