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MGMT 和全基因组 DNA 甲基化对多形性胶质母细胞瘤的诊断、预后和治疗的影响。

MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.

机构信息

CEINGE-Advanced Biotechnologies, Via G. Salvatore 486, 80145 Napoli, Italy.

Department of Molecular Medicine and Medical Biotechnologies, University of Napoli "Federico II", Via S. Pansini 5, 80131 Napoli, Italy.

出版信息

Int J Mol Sci. 2022 Jun 27;23(13):7148. doi: 10.3390/ijms23137148.

DOI:10.3390/ijms23137148
PMID:35806153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9266959/
Abstract

Epigenetic changes in DNA methylation contribute to the development of many diseases, including cancer. In glioblastoma multiforme, the most prevalent primary brain cancer and an incurable tumor with a median survival time of 15 months, a single epigenetic modification, the methylation of the () gene, is a valid biomarker for predicting response to therapy with alkylating agents and also, independently, prognosis. More recently, the progress from single gene to whole-genome analysis of DNA methylation has allowed a better subclassification of glioblastomas. Here, we review the clinically relevant information that can be obtained by studying gene and whole-genome DNA methylation changes in glioblastomas, also highlighting benefits, including those of liquid biopsy, and pitfalls of the different detection methods. Finally, we discuss how changes in DNA methylation, especially in glioblastomas bearing mutations in the genes, can be exploited as targets for tailoring therapy.

摘要

DNA 甲基化的表观遗传改变导致了许多疾病的发生,包括癌症。在多形性胶质母细胞瘤中,最常见的原发性脑癌和一种无法治愈的肿瘤,中位生存时间为 15 个月,一个单一的表观遗传修饰,即 () 基因的甲基化,是预测对烷基化剂治疗反应的有效生物标志物,并且独立地预测预后。最近,从单个基因到全基因组 DNA 甲基化分析的进展使得对胶质母细胞瘤进行更好的亚分类成为可能。在这里,我们回顾了通过研究胶质母细胞瘤中的 () 基因和全基因组 DNA 甲基化变化可以获得的临床相关信息,同时强调了不同检测方法的优势,包括液体活检的优势,以及缺陷。最后,我们讨论了 DNA 甲基化的变化,特别是在携带 () 基因突变的胶质母细胞瘤中,如何可以被用作定制治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6429/9266959/238ca8163d7b/ijms-23-07148-g004.jpg
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