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脑膜瘤中甲基化特异性多重连接依赖探针扩增技术

Methylation-specific multiplex ligation-dependent probe amplification in meningiomas.

作者信息

Ewald Christian, Hofmann Thomas, Kuhn Susanne A, Deufel Thomas, Beetz Christian, Kalff Rolf

机构信息

Klinik für Neurochirurgie, Universitätsklinikum, Jena, Germany.

出版信息

J Neurooncol. 2008 Dec;90(3):267-73. doi: 10.1007/s11060-008-9672-8. Epub 2008 Sep 2.

Abstract

Genomic loss and promotor methylation contribute to inactivation of tumor suppressor genes (TSGs). Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a relatively new method for simultaneous detection of both these alterations. Here, we apply MS-MLPA to a series of 15 meningiomas of different WHO grades. The two MS-MLPA probe sets used detect copy number changes in 55 unselected TSGs and promotor methylation in a subset of 36 of these genes. Our findings concerning genomic deletions are concordant with previously published studies using alternative techniques. The number of aberrations identified per tumor increased with histopathologically determined grading. The most frequent single event was deletion of the von Hippel-Lindau (VHL) gene in 12 of the 15 tumors. Moreover, VHL deletion status was associated with presence/absence of peritumoral edema. Methylation was rare, being observed in only four tumors and in each case restricted to a single gene. We conclude that a meningioma-specific MS-MLPA probe set would be a valuable tool for both research and diagnostic approaches in these tumors.

摘要

基因组缺失和启动子甲基化会导致肿瘤抑制基因(TSGs)失活。甲基化特异性多重连接依赖探针扩增技术(MS-MLPA)是一种相对较新的可同时检测这两种改变的方法。在此,我们将MS-MLPA应用于一系列15例不同世界卫生组织(WHO)分级的脑膜瘤。所使用的两个MS-MLPA探针组可检测55个未选定的TSGs的拷贝数变化以及其中36个基因亚组的启动子甲基化情况。我们关于基因组缺失的研究结果与先前使用其他技术发表的研究结果一致。每个肿瘤中检测到的畸变数量随组织病理学确定的分级增加。最常见的单一事件是15个肿瘤中有12个出现了冯·希佩尔-林道(VHL)基因缺失。此外,VHL缺失状态与瘤周水肿的有无相关。甲基化情况较为罕见,仅在4个肿瘤中观察到,且每种情况下都仅限于单个基因。我们得出结论,针对脑膜瘤特异性的MS-MLPA探针组对于这些肿瘤的研究和诊断方法而言将是一种有价值的工具。

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