Martinez Ramon, Schackert Gabriele
Department of Neurosurgery, University of Dresden, Dresden, Germany.
Epigenetics. 2007 Jul-Sep;2(3):147-50. doi: 10.4161/epi.2.3.5049. Epub 2007 Sep 15.
Malignant gliomas and specially glioblastoma multiforme are the most frequent and devastating brain tumors in adults. Intensive molecular and cytogenetical studies have revealed a wide variety of deregulated genes implicated in cell cycles, DNA repair, apoptosis, cell migration, invasion and angiogenesis with little translational success. An increasing number of reports investigating epigenetic injuries in malignant gliomas have been recently published, although the panorama of CpG island aberrant hypermethylation, histone modification and chromatin states in these lethal tumors is only partially devised. In the present analysis, we discuss the magnitude and significance of epigenetic lesions in the pathogenesis and mechanisms of progression of malignant gliomas as well as their influence on patient survival. The new venue of epigenetic research provides tools for the identification of genes differentially methylated that may be implicated in tumorigenesis and furthermore, epigenetics-based drugs may constitute a promising alternative resource of therapy for this, to the moment, incurable malignancy.
恶性胶质瘤，特别是多形性胶质母细胞瘤，是成人中最常见且最具破坏性的脑肿瘤。深入的分子和细胞遗传学研究揭示了多种与细胞周期、DNA修复、细胞凋亡、细胞迁移、侵袭及血管生成相关的失调基因，但转化应用方面成效甚微。最近，越来越多关于恶性胶质瘤表观遗传损伤的研究报告发表，尽管这些致命肿瘤中CpG岛异常高甲基化、组蛋白修饰和染色质状态的全貌仅得到部分揭示。在本分析中，我们讨论了表观遗传损伤在恶性胶质瘤发病机制和进展过程中的程度及意义，以及它们对患者生存的影响。表观遗传学研究的新领域为鉴定可能与肿瘤发生相关的差异甲基化基因提供了工具，此外，基于表观遗传学的药物可能成为治疗这种目前无法治愈的恶性肿瘤的一种有前景的替代资源。
