Batora N V, Sturm D, Jones D T W, Kool M, Pfister S M, Northcott P A
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany; Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
Neuroscience. 2014 Apr 4;264:171-85. doi: 10.1016/j.neuroscience.2013.07.030. Epub 2013 Jul 20.
Recent advances in genomic technologies have allowed for tremendous progress in our understanding of the biology underlying medulloblastoma, a malignant childhood brain tumor. Consensus molecular subgroups have been put forth by the pediatric neuro-oncology community and next-generation genomic studies have led to an improved description of driver genes and pathways somatically altered in these subgroups. In contrast to the impressive pace at which advances have been made at the level of the medulloblastoma genome, comparable studies of the epigenome have lagged behind. Complementary data yielded from genomic sequencing and copy number profiling have verified frequent targeting of chromatin modifiers in medulloblastoma, highly suggestive of prominent epigenetic deregulation in the disease. Past studies of DNA methylation-dependent gene silencing and microRNA expression analyses further support the concept of medulloblastoma as an epigenetic disease. In this Review, we aim to summarize the key findings of past reports pertaining to medulloblastoma epigenetics as well as recent and ongoing genomic efforts linking somatic alterations of the genome with inferred deregulation of the epigenome. In addition, we predict what is on the horizon for medulloblastoma epigenetics and how aberrant changes in the medulloblastoma epigenome might serve as an attractive target for future therapies.
基因组技术的最新进展使我们在了解髓母细胞瘤（一种儿童恶性脑肿瘤）的生物学基础方面取得了巨大进展。儿科神经肿瘤学界已经提出了共识分子亚组，下一代基因组研究对这些亚组中体细胞改变的驱动基因和信号通路进行了更完善的描述。与髓母细胞瘤基因组层面取得进展的惊人速度相比，表观基因组的相关研究则滞后了。基因组测序和拷贝数分析产生的补充数据证实了髓母细胞瘤中染色质修饰因子的频繁靶向作用，强烈提示该疾病存在显著的表观遗传失调。过去关于DNA甲基化依赖性基因沉默和微小RNA表达分析的研究进一步支持了髓母细胞瘤是一种表观遗传疾病的概念。在本综述中，我们旨在总结过去有关髓母细胞瘤表观遗传学报告的关键发现，以及近期和正在进行的将基因组体细胞改变与推断的表观基因组失调联系起来的基因组研究工作。此外，我们预测髓母细胞瘤表观遗传学的未来发展方向，以及髓母细胞瘤表观基因组的异常变化如何可能成为未来治疗的有吸引力的靶点。
