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NAT MED：弥漫性内皮神经胶质瘤全新治疗靶点

2017-03-14 MedSci MedSci原创

弥漫性内皮神经胶质瘤赖氨酸-甲硫氨酸置换Ezh2
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我们发现在DIPG小鼠模型中和在表达H3K27M的人原代DIPGH3K27me3基因之间的高度同源。最后，这些结果显示残留的PRC2活性是表达H3K27M的DIPG的增殖所需要的，并且EZH2是用于治疗这些肿瘤的潜在治疗靶点。

弥漫性内皮神经胶质瘤（DIPG）是一种高度危险的儿科脑干肿瘤，其特征是快速和渐进性导致患者死亡。在超过80％的这类肿瘤中组蛋白H3的杂合位点发生突变，并导致赖氨酸 - 甲硫氨酸置换（H3K27M）。

这种组蛋白突变体的表达伴随着多梳抑制复合物（PRC2）介导的H3K27三甲基化（H3K27me3）水平的降低，这被认为是DIPG肿瘤发生的促进原因。

尽管发现H3K27me3的水平降低，但我们仍然在H3K27M6，7阳性的DIPG细胞中检测到PRC2活性。在这里我们构建了DIPG的小鼠模型，其中H3K27M加强肿瘤发生。使用此模型和原发性患者来源的DIPG细胞系，我们发现H3K27M导致肿瘤需要PRC2增殖。此外，我们证明小分子EZH2抑制剂抑制肿瘤细胞生长通过依赖于肿瘤抑制蛋白p16INK4A的诱导机制。全基因组富集分析显示H3K27M细胞中带有H3K27me3的基因是易富集目标。此外，我们发现在DIPG小鼠模型中和在表达H3K27M的人原代DIPGH3K27me3基因之间的高度同源。最后，这些结果显示残留的PRC2活性是表达H3K27M的DIPG的增殖所需要的，并且EZH2是用于治疗这些肿瘤的潜在治疗靶点。

原始出处：
Mohammad F, Weissmann S, Leblanc B, et al. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas[J]. Nature Medicine, 27 February 2017.doi:10.1038/nm.4293

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    2017-07-06 drj2003

    #治疗靶点#

    0

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    2017-08-28 liye789132251

    #Nat#

    0

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    2017-06-15 swallow

    #皮神经#

    0

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    2017-03-16 卡圣

    好好学习，好文章谢谢分享

    0

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    2017-03-16 bsmagic9132

    #神经胶质瘤#

    0

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    2017-03-16 zhouqu_8

    #弥漫性#

    0

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    2017-03-16 ms3994565386320060

    #Med#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1895328, encodeId=f152189532804, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Thu Jul 06 15:05:00 CST 2017, time=2017-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1881744, encodeId=552f1881e4405, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Aug 28 08:05:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1998431, encodeId=93431998431cb, content=<a href='/topic/show?id=3c6be197917' target=_blank style='color:#2F92EE;'>#皮神经#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71979, encryptionId=3c6be197917, topicName=皮神经)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=83a4244, createdName=swallow, createdTime=Thu Jun 15 08:05:00 CST 2017, time=2017-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=180252, encodeId=839f180252d1, content=好好学习，好文章谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOWcPEsEP4FrvDcicue5V6rMkmXmY73KjYP59vQrEdjU89iaN4ZkOhsItlHkmGTjhV3b5S3zOQA4E0/0, createdBy=cc261682151, createdName=卡圣, createdTime=Thu Mar 16 08:06:07 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315080, encodeId=e9c11315080ca, content=<a href='/topic/show?id=0a08e451815' target=_blank style='color:#2F92EE;'>#神经胶质瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74518, encryptionId=0a08e451815, topicName=神经胶质瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3eaf430, createdName=bsmagic9132, createdTime=Thu Mar 16 05:05:00 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438566, encodeId=524714385666b, content=<a href='/topic/show?id=9851500416c' target=_blank style='color:#2F92EE;'>#弥漫性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50041, encryptionId=9851500416c, topicName=弥漫性)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Mar 16 05:05:00 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1607299, encodeId=cb39160e299a1, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Mar 16 05:05:00 CST 2017, time=2017-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=179965, encodeId=678c1e996502, content=学习了，谢谢了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOWcPEsEP4FrvDcicue5V6rMkmXmY73KjYP59vQrEdjU89iaN4ZkOhsItlHkmGTjhV3b5S3zOQA4E0/0, createdBy=cc261682151, createdName=卡圣, createdTime=Wed Mar 15 06:50:43 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-03-15 卡圣

    学习了，谢谢了

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