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腾讯登录Nature:不同子群成神经管细胞瘤基因突变新发现
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<div>6月20日，<em>N... |
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<div>6月20日，<em>Nature</em>杂志在线报道，通过对不同子群成神经管细胞瘤患者的研究，科学家发现了成神经管细胞瘤中一系列与表观遗传修饰和祖细胞发育有关的基因突变。</div>
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成神经管细胞瘤是儿童恶性脑肿瘤，其中包括4个离散子群。为确定突变驱动成神经管细胞瘤，研究者对37例肿瘤患者的全基因组测序并和正常的血液基因组测序结果相匹配比较。在上述研究中发现了一百三十六个在体细胞中存在突变的基因，然后又在56例成神经管细胞患者中对这些突变基因进行测序验证。
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结果新发现了41个过去未知与成神经管细胞瘤相关的基因突变。其中一些基因突变的靶点涉及不同的患者子群的表观遗传调节组成部分，如在成神经管细胞瘤患者子群3和4中的H3K27和H3K4三重甲基化的调节因子；成神经管细胞瘤患者Wnt信号 - 子群中的CTNNB1相关的染色质重构因子等。通过实验诱导小鼠菱形唇祖细胞的某些基因突变，以生成Wnt信号 - 子群的肿瘤，研究者发现了保持细胞系（DDX3X）的基因，以及在肿瘤发生过程中启动CDH1基因或与PIK3CA基因相互作用的基因突变。
这些数据揭示了不同子群成神经管细胞瘤患者的重要发病机理并为近一步的靶向性治疗提供了重要参考。
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<img src="http://www.bioon.com/biology/UploadFiles/201206/2012062109173849.jpg" alt="" width="113" height="149" border="0" hspace="0" />
<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://dx.doi.org/10.1038/nature11213" target="_blank">10.1016/j.cell.2011.10.017</a>
PMC:
PMID:
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<br/><strong>Novel mutations target distinct subgroups of medulloblastoma</strong><br/>
Giles Robinson,1, 2, 3, 20 Matthew Parker,1, 4, 20 Tanya A. Kranenburg,1, 2, 20 Charles Lu,1, 5 Xiang Chen,1, 4 Li Ding,1, 5, 6 Timothy N. Phoenix,1, 2 Erin Hedlund,1, 4 Lei Wei,1, 4, 7 Xiaoyan Zhu,1, 2 Nader Chalhoub,1, 2 Suzanne J. Baker,1, 2 Robert Huether,1, 4, 8 Richard Kriwacki,1, 8 Natasha Curley,1, 2 Radhika Thiruvenkatam,1, 2 Jianmin Wang,1, 9 Gang Wu,1, 4 Michael Rusch,1, 4 Xin Hong,1, 5 Jared Becksfort,1, 9 Pankaj Gupta,1, 9 Jing Ma,1, 7 John Easton,1, 4 Bhavin Vadodaria,1, 4 Arzu Onar-Thomas,1, 10 Tong Lin,1, 10 Shaoyi Li,1, 10 Stanley Pounds,1, 10 Steven Paugh,1, 11 David Zhao,1, 9 Daisuke Kawauchi,1, 12 Martine F. Roussel,1, 12 David Finkelstein,1, 4 David W. Ellison,1, 7 Ching C. Lau,1, 13 Eric Bouffet,1, 14 Tim Hassall,1, 15 Sridharan Gururangan,1, 16 Richard Cohn,1, 17 Robert S. Fulton,1, 5, 6 Lucinda L. Fulton,1, 5, 6 David J. Dooling,1, 5, 6 Kerri Ochoa,1, 5, 6 Amar Gajjar,1, 3 Elaine R. Mardis,1, 5, 6, 18 Richard K. Wilson,1, 5, 6, 19 James R. Downing,1, 7 Jinghui Zhang1, 4 & Richard J. Gilbertson1, 2, 3 et al.
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.
<br/>来源：生物谷
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<div> </div>
<!-- 开始 文章标题部分 -->
<div id="region-column1and2-layout2">
<div>6月20日，<em>Nature</em>杂志在线报道，通过对不同子群成神经管细胞瘤患者的研究，科学家发现了成神经管细胞瘤中一系列与表观遗传修饰和祖细胞发育有关的基因突变。</div>
</div>
<div id="region-column1and2-layout2">
成神经管细胞瘤是儿童恶性脑肿瘤，其中包括4个离散子群。为确定突变驱动成神经管细胞瘤，研究者对37例肿瘤患者的全基因组测序并和正常的血液基因组测序结果相匹配比较。在上述研究中发现了一百三十六个在体细胞中存在突变的基因，然后又在56例成神经管细胞患者中对这些突变基因进行测序验证。
<!--more-->
结果新发现了41个过去未知与成神经管细胞瘤相关的基因突变。其中一些基因突变的靶点涉及不同的患者子群的表观遗传调节组成部分，如在成神经管细胞瘤患者子群3和4中的H3K27和H3K4三重甲基化的调节因子；成神经管细胞瘤患者Wnt信号 - 子群中的CTNNB1相关的染色质重构因子等。通过实验诱导小鼠菱形唇祖细胞的某些基因突变，以生成Wnt信号 - 子群的肿瘤，研究者发现了保持细胞系（DDX3X）的基因，以及在肿瘤发生过程中启动CDH1基因或与PIK3CA基因相互作用的基因突变。
这些数据揭示了不同子群成神经管细胞瘤患者的重要发病机理并为近一步的靶向性治疗提供了重要参考。
<div id="ztload">
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012062109173849.jpg" alt="" width="113" height="149" border="0" hspace="0" />
<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://dx.doi.org/10.1038/nature11213" target="_blank">10.1016/j.cell.2011.10.017</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Novel mutations target distinct subgroups of medulloblastoma</strong><br/>
Giles Robinson,1, 2, 3, 20 Matthew Parker,1, 4, 20 Tanya A. Kranenburg,1, 2, 20 Charles Lu,1, 5 Xiang Chen,1, 4 Li Ding,1, 5, 6 Timothy N. Phoenix,1, 2 Erin Hedlund,1, 4 Lei Wei,1, 4, 7 Xiaoyan Zhu,1, 2 Nader Chalhoub,1, 2 Suzanne J. Baker,1, 2 Robert Huether,1, 4, 8 Richard Kriwacki,1, 8 Natasha Curley,1, 2 Radhika Thiruvenkatam,1, 2 Jianmin Wang,1, 9 Gang Wu,1, 4 Michael Rusch,1, 4 Xin Hong,1, 5 Jared Becksfort,1, 9 Pankaj Gupta,1, 9 Jing Ma,1, 7 John Easton,1, 4 Bhavin Vadodaria,1, 4 Arzu Onar-Thomas,1, 10 Tong Lin,1, 10 Shaoyi Li,1, 10 Stanley Pounds,1, 10 Steven Paugh,1, 11 David Zhao,1, 9 Daisuke Kawauchi,1, 12 Martine F. Roussel,1, 12 David Finkelstein,1, 4 David W. Ellison,1, 7 Ching C. Lau,1, 13 Eric Bouffet,1, 14 Tim Hassall,1, 15 Sridharan Gururangan,1, 16 Richard Cohn,1, 17 Robert S. Fulton,1, 5, 6 Lucinda L. Fulton,1, 5, 6 David J. Dooling,1, 5, 6 Kerri Ochoa,1, 5, 6 Amar Gajjar,1, 3 Elaine R. Mardis,1, 5, 6, 18 Richard K. Wilson,1, 5, 6, 19 James R. Downing,1, 7 Jinghui Zhang1, 4 & Richard J. Gilbertson1, 2, 3 et al.
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.
<br/>来源：生物谷
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