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通过劫持增强子发生的肿瘤形成过程

摘要 : 德国癌症研究中心(DKFZ)领导的一个国际研究组在新研究中,发现“增强子劫持”是一种儿童癌症中驱动致癌基因激活的一个高效机制。相关文章发表于2014年6月22日的《Nature》杂志上。

成神经管细胞瘤是一种高度恶性的儿童脑肿瘤。

本文作者集中关注两个没有很好表征的亚型,即group 3 和 group 4,它们占儿童病例的绝大多数。他们识别出限于这两个亚型的普遍性基因组结构变异体,并将原致癌基因GFI1 和GFI1B的编码区域与导致致癌基因激活的增强子元素结合了起来。

这项研究将“增强子劫持”识别为在一种儿童癌症中驱动致癌基因激活的一个高效机制。

原文摘要:

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

Paul A. Northcott, Catherine Lee, Thomas Zichner, Adrian M. Stütz, Serap Erkek, Daisuke Kawauchi, David J. H. Shih, Volker Hovestadt, Marc Zapatka, Dominik Sturm, David T. W. Jones, Marcel Kool, Marc Remke, Florence M. G. Cavalli, Scott Zuyderduyn, Gary D. Bader, Scott VandenBerg, Lourdes Adriana Esparza, Marina Ryzhova, Wei Wang, Andrea Wittmann, Sebastian Stark, Laura Sieber, Huriye Seker-Cin, Linda linke et al.

Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate ‘enhancer hijacking’ as an efficient mechanism driving oncogene activation in a childhood cancer.

对应Nature杂志: 2014年7月24日Nature杂志精选

来源: Nature中文 浏览次数:62

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