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Nat Genet：外显子测序显示数种体细胞突变可导致子宫内膜癌

2012-11-26 Daphne Bell 《自然—遗传学》

子宫内膜肿瘤体细胞突变
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　　近期发表的《自然—遗传学》报道了数种可影响子宫内膜，导致子宫内膜癌发生的复发性体细胞突变。 　　子宫内膜癌是世界第六大女性常见癌症。Daphne Bell等人对13种主要的浆液性子宫内膜肿瘤进行了外显子测序。他们对18种基因进行患病筛查，发现另有40种浆液性子宫内膜肿瘤存在复发性。通过主要 组织学亚型的比较，Bell和同事在23个透明细胞、67个子宫内膜样本和18个混合型子宫内膜肿瘤对

　　近期发表的《自然—遗传学》报道了数种可影响子宫内膜，导致子宫内膜癌发生的复发性体细胞突变。

　　子宫内膜癌是世界第六大女性常见癌症。Daphne Bell等人对13种主要的浆液性子宫内膜肿瘤进行了外显子测序。他们对18种基因进行患病筛查，发现另有40种浆液性子宫内膜肿瘤存在复发性。通过主要 组织学亚型的比较，Bell和同事在23个透明细胞、67个子宫内膜样本和18个混合型子宫内膜肿瘤对上述基因的3种进行了外显子测序。他们确定，与泛素 连接酶复合物的染色质重构有着密切关联的体细胞突变具有高突变频率，而且他们认为这些突变在子宫内膜癌发病机理中具有重要作用。

原始链接：

Le Gallo M, O'Hara AJ, Rudd ML, Urick ME, Hansen NF, O'Neil NJ, Price JC, Zhang S, England BM, Godwin AK, Sgroi DC; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter P, Mullikin JC, Merino MJ, Bell DW.Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.

Nat Genet. 2012 Oct 28. doi: 10.1038/ng.2455. [Epub ahead of print]

外显子测序相关文献:

Nature Genetics：大批量小细胞肺癌外显子组测序完成

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Nat Genetics：与肝吸虫有关胆管癌的外显子测序结果公布

Nature：全外显子组测序的技术发现高血压发病机制

2012国际卒中大会：全外显子测序用于家族性颅内动脉瘤基因变异评估 

全外显子测序揭示家族性颅内动脉瘤基因变异

小知识:外显子测序

　外显子测序（也称目标外显子组捕获）是指利用序列捕获技术将全基因组外显子区域DNA捕捉并富集后进行高通量测序的基因组分析方法。是一种选择基因组的编码序列的高校策略，外显子测序相对于基因组重测序成本较低，对研究已知基因的SNP、Indel等具有较大的优势。[1] 外显子(expressed region)是真核生物基因的一部分，它在剪接(Splicing)后仍会被保存下来，并可在蛋白质生物

  图1，外显子测序

合成过程中被表达为蛋白质。外显子是最后出现在成熟RNA中的基因序列，又称表达序列。既存在于最初的转录产物中，也存在于成熟的RNA分子中的核苷酸序列。在人类基因中大约有180,000外显子，占人类基因组的1%，约30MB。 　　外显子组测序是确定罕见的孟德尔遗传疾病的因果变化高效策略。 　　它的高效由以下几个因素促成： 　　1、定位克隆，降低功耗，成功地确定罕见变异， 　　2、大部分导致孟德尔遗传紊乱的基因变异是通过破坏蛋白质编码形成的，

  图2，外显子测序

　　3、大量的非同义替换是有害的， 　　4、剪接位点也代表序列的主要功能的变化。 　　外显子组测序的流程如图1、图2所示。

相关资料:
外显子基因捕获.pdf
全基因组外显子测序及其应用.pdf

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    2013-03-30 liye789132251

    #Nat#

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    2012-12-18 cy0324

    #Gene#

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beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42862, encryptionId=492a42862bd, topicName=外显子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=)]
    2013-11-09 canlab

    #NET#

    0

  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556308, encodeId=1be7155630840, content=<a href='/topic/show?id=17d742864ea' target=_blank style='color:#2F92EE;'>#外显子测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42864, encryptionId=17d742864ea, topicName=外显子测序)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ee014741656, createdName=jinweidong, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619013, encodeId=17ec161901330, content=<a href='/topic/show?id=492a42862bd' target=_blank style='color:#2F92EE;'>#外显子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42862, encryptionId=492a42862bd, topicName=外显子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=)]
    2012-12-21 12498974m61暂无昵称

    #内膜#

    0

  5. 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createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556308, encodeId=1be7155630840, content=<a href='/topic/show?id=17d742864ea' target=_blank style='color:#2F92EE;'>#外显子测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42864, encryptionId=17d742864ea, topicName=外显子测序)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ee014741656, createdName=jinweidong, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619013, encodeId=17ec161901330, content=<a href='/topic/show?id=492a42862bd' target=_blank style='color:#2F92EE;'>#外显子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42862, encryptionId=492a42862bd, topicName=外显子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=)]
    2013-08-01 江川靖瑶

    #Genet#

    0

  6. 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encryptionId=4c2d3051535, topicName=内膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=730431558473, createdName=12498974m61暂无昵称, createdTime=Fri Dec 21 07:30:00 CST 2012, time=2012-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685871, encodeId=09ca16858e178, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e128296421, createdName=江川靖瑶, createdTime=Thu Aug 01 22:30:00 CST 2013, time=2013-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1946345, encodeId=0fa11946345f3, content=<a href='/topic/show?id=634e2664446' target=_blank style='color:#2F92EE;'>#体细胞突变#</a>, beContent=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556308, encodeId=1be7155630840, content=<a href='/topic/show?id=17d742864ea' target=_blank style='color:#2F92EE;'>#外显子测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42864, encryptionId=17d742864ea, topicName=外显子测序)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ee014741656, createdName=jinweidong, createdTime=Wed Nov 28 00:30:00 CST 2012, time=2012-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619013, encodeId=17ec161901330, content=<a href='/topic/show?id=492a42862bd' target=_blank style='color:#2F92EE;'>#外显子#</a>, 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    2013-07-06 ms7514935887898259

    #体细胞突变#

    0

  7. 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    2012-11-28 zhouqu_8

    #体细胞#

    0

  8. 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    2012-11-28 jinweidong

    #外显子测序#

    0

  9. 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    2012-11-28 docwu2019

    #外显子#

    0