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恶性胶质瘤中异常的CpG岛高甲基化谱

Aberrant CpG islands hypermethylation profiles in malignant gliomas.

作者信息

Kim Kwang Ryeol, Kim Ealmaan, Son Eun Ik

机构信息

Department of Neurosurgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.

出版信息

Brain Tumor Res Treat. 2014 Apr;2(1):29-35. doi: 10.14791/btrt.2014.2.1.29. Epub 2014 Apr 29.

Abstract

BACKGROUND

The authors analyzed whether the promoter hypermethylation of cancer-related genes was involved in the tumorigenesis of malignant gliomas.

METHODS

A total of 29 patients received surgery and histologically confirmed to have malignant gliomas from January 2000 to December 2006. The promoter methylation status of several genes, which were reported to be frequently methylated in malignant gliomas, was investigated using methylation-specific polymerase chain reaction.

RESULTS

All cases of malignant gliomas represented the promoter hypermethylation in at least 2 or more genes tested. Of 29 tumors, 28 (96.55%) showed concurrent hypermethylation of 3 or more genes. Ras association domain family member 1, epithelial cadherin, O-6 methyl guanine DNA methyltransferase, thrombospondin 1, p14 and adenomatous polyposis coli were frequently methylated in high grade gliomas including glioblastomas, anaplastic astrocytomas, and anaplastic oligodendrogliomas.

CONCLUSION

Aberrant hypermethylation profile was closely related with malignant gliomas suggesting that epigenetic change may play a role in the development of malignant gliomas. Two or three target genes may provide useful clues to the development of the useful prognostic as well as diagnostic assays for malignant gliomas.

摘要

背景

作者分析了癌症相关基因的启动子高甲基化是否参与恶性胶质瘤的肿瘤发生过程。

方法

2000年1月至2006年12月期间,共有29例接受手术且经组织学确诊为恶性胶质瘤的患者。使用甲基化特异性聚合酶链反应研究了几个据报道在恶性胶质瘤中经常发生甲基化的基因的启动子甲基化状态。

结果

所有恶性胶质瘤病例在至少2个或更多检测基因中均表现出启动子高甲基化。在29个肿瘤中,28个(96.55%)显示3个或更多基因同时发生高甲基化。Ras关联结构域家族成员1、上皮钙黏蛋白、O-6甲基鸟嘌呤DNA甲基转移酶、血小板反应蛋白1、p14和腺瘤性息肉病基因在包括胶质母细胞瘤、间变性星形细胞瘤和间变性少突胶质细胞瘤在内的高级别胶质瘤中经常发生甲基化。

结论

异常的高甲基化谱与恶性胶质瘤密切相关,提示表观遗传变化可能在恶性胶质瘤的发生发展中起作用。两到三个靶基因可能为开发有用的恶性胶质瘤预后及诊断检测方法提供有用线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eed/4049560/6fedf43334df/btrt-2-29-g001.jpg

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