The Role of Chromatin Remodeling in Medulloblastoma
The Role of Chromatin Remodeling in Medulloblastoma
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DOI：
10.1111/bpa.12019
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发表时间：
2013-03-01
期刊：
影响因子：
6.4
通讯作者：
Pfister, Stefan M.
中科院分区：
文献类型：
--
作者：
Jones, David T. W.;Northcott, Paul A.;Pfister, Stefan M.
染色质机制改变的频率和普遍性出人意料地高，这是从目前泛滥的癌症基因组数据中出现的最引人注目的主题之一。髓母细胞瘤(MB)是一种恶性的儿童脑肿瘤，也不例外，最近的大量研究表明，在染色质加工的各个水平上都发生了多重改变。MB现在通常被认为是由四个主要分子实体(WNT、SHH、第3族和第4族)组成的，它们的临床和生物学特性各不相同。这些亚组之间的相似和不同也反映在每一组中被发现改变的特定染色质修饰物上，并且每个新的癌症基因组序列或微阵列图谱都在这一重要的知识库中添加。这些数据正在从根本上改变我们对肿瘤发展途径的理解，不仅是对MB，而且对整个癌症都是如此。它们还为开发合理的、个性化的治疗方法提供了一类新的靶点。这些染色质重构体在MB中失控的机制，以及对未来基础研究和临床应用的影响，将在这里进行研究。
The unexpectedly high frequency and universality of alterations to the chromatin machinery is one of the most striking themes emerging from the current deluge of cancer genomics data. Medulloblastoma (MB), a malignant pediatric brain tumor, is no exception to this trend, with a wealth of recent studies indicating multiple alterations at all levels of chromatin processing. MB is typically now regarded as being composed of four major molecular entities (WNT, SHH, Group 3 and Group 4), which vary in their clinical and biological characteristics. Similarities and differences across these subgroups are also reflected in the specific chromatin modifiers that are found to be altered in each group, and each new cancer genome sequence or microarray profile is adding to this important knowledge base. These data are fundamentally changing our understanding of tumor developmental pathways, not just for MB but also for cancer as a whole. They also provide a new class of targets for the development of rational, personalized therapeutic approaches. The mechanisms by which these chromatin remodelers are dysregulated in MB, and the consequences both for future basic research and for translation to the clinic, will be examined here.