Department of Neurosurgery, University of Goettingen, Germany.
Neurobiol Dis. 2010 Jul;39(1):40-6. doi: 10.1016/j.nbd.2009.12.030. Epub 2010 Jan 11.
Glioblastoma multiforme (GBM) is the most frequent brain tumor in adults. This lethal cancer is a challenge in neuro-oncology since patients almost invariably succumb to the disease. Intensive molecular studies have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration, angiogenesis and cell cycle. Recent investigation of epigenetic lesions in GBM have led to a more comprehensive understanding of this malignancy and even to target therapies, including the milestone of temozolomide chemotherapy, which makes possible a better outcome for GBM patients with hypermethylated MGMT. Nevertheless, the whole scenario including global hypomethylation, aberrant promoter hypermethylation, histone modification and chromatin states in GBM has only been partially revealed. We discuss the magnitude of epigenetic alterations in the pathogenesis of GBM and their translational relevance to patient survival.
胶质母细胞瘤(GBM)是成人中最常见的脑肿瘤。这种致命的癌症是神经肿瘤学的一个挑战,因为患者几乎无一例外地死于该疾病。密集的分子研究揭示了涉及 DNA 修复、细胞凋亡、细胞迁移、血管生成和细胞周期的各种失调的遗传途径。最近对 GBM 中表观遗传损伤的研究使人们对这种恶性肿瘤有了更全面的认识,甚至可以进行靶向治疗,包括替莫唑胺化疗这一里程碑式的治疗方法,使 MGMT 高甲基化的 GBM 患者有更好的预后。然而,GBM 中包括全局低甲基化、异常启动子高甲基化、组蛋白修饰和染色质状态在内的整个表观遗传学改变的全貌仅被部分揭示。我们讨论了表观遗传学改变在 GBM 发病机制中的重要性及其对患者生存的转化相关性。