文章：

儿童和成人胶质母细胞瘤：多形式（epi）基因组罪魁祸首出现

Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge

原文发布日期：2014-01-24

DOI: 10.1038/nrc3655

类型: Review Article

开放获取: 否

要点：

1. Glioblastoma is the most frequent and most aggressive malignant primary brain tumour and remains almost universally incurable in both children and adults.
2. Comprehensive molecular profiling studies have greatly broadened our knowledge of the underlying genomic and epigenomic aberrations that are associated with glioblastoma initiation and progression.
3. Genetic lesions result in disrupted epigenetic control mechanisms by altering histone modifications, DNA methylation and gene expression patterns in a large proportion of glioblastomas.
4. Based on recurrent combinations of genomic and/or epigenomic features with distinct patient characteristics, glioblastomas across all ages are being divided into meaningful biological subgroups, which are likely to guide the design of future clinical trials.
5. The complex interplay between the glioblastoma genome and epigenome opens the way for the development of novel innovative therapeutic strategies that are urgently needed to tackle this deadly brain tumour.

要点翻译：

1. 胶质母细胞瘤是最常见、最具侵袭性的恶性原发性脑肿瘤，且无论儿童或成人患者几乎均无法治愈。
2. 全面的分子谱研究极大地拓宽了我们对胶质母细胞瘤发生发展相关基因组和表观基因组异常的认识。
3. 基因损伤通过改变组蛋白修饰、DNA甲基化和基因表达模式，导致大部分胶质母细胞瘤的表观遗传调控机制紊乱。
4. 基于基因组和/或表观基因组特征与特定患者临床表现的反复组合，所有年龄段的胶质母细胞瘤正被划分为有意义的生物学亚组，这有望指导未来临床试验的设计。
5. 胶质母细胞瘤基因组与表观基因组之间复杂的相互作用，为开发应对这一致命脑肿瘤所亟需的创新治疗策略开辟了新途径。

英文摘要：

We have extended our understanding of the molecular biology that underlies adult glioblastoma over many years. By contrast, high-grade gliomas in children and adolescents have remained a relatively under-investigated disease. The latest large-scale genomic and epigenomic profiling studies have yielded an unprecedented abundance of novel data and provided deeper insights into gliomagenesis across all age groups, which has highlighted key distinctions but also some commonalities. As we are on the verge of dissecting glioblastomas into meaningful biological subgroups, this Review summarizes the hallmark genetic alterations that are associated with distinct epigenetic features and patient characteristics in both paediatric and adult disease, and examines the complex interplay between the glioblastoma genome and epigenome.

摘要翻译： 

多年来，我们对成人胶质母细胞瘤分子生物学基础的认识已不断深入。相比之下，儿童和青少年高级别胶质瘤仍是一种研究相对不足的疾病。最新的大规模基因组与表观基因组分析研究带来了前所未有的大量新数据，为各年龄段的胶质瘤发生机制提供了更深刻的洞察，突出了关键差异，也揭示了一些共性。随着我们即将把胶质母细胞瘤划分为有意义的生物学亚群，本综述总结了儿童和成人疾病中与特异性表观遗传特征及患者特征相关的标志性遗传改变，并探讨了胶质母细胞瘤基因组与表观基因组之间复杂的相互作用。

原文链接：

Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge