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Nat Genet:近10000例前瞻性肿瘤靶向测序,MSK-IMPACT揭示近30%的肿瘤存在全基因组倍增(WGD)

2018-07-17 genegogo 生信者言

2018年7月16日,来自纪念斯隆-凯特琳癌症中心(MSKCC)的研究人员在Nature Genetics杂志发表文章,描述了全基因组倍增(WGD,whole-genome doubling)在不同癌症类型和亚型中的动态作用。

2018年7月16日,来自纪念斯隆-凯特琳癌症中心(MSKCC)的研究人员在Nature Genetics杂志发表文章,描述了全基因组倍增(WGD,whole-genome doubling)在不同癌症类型和亚型中的动态作用。

该团队使用MSK-IMPACT测序平台对来自9,692个晚期癌症病例(含55种肿瘤类型)的肿瘤样本和血液配对样本进行靶向测序,结果发现,近30%的肿瘤病例中存在全基因组倍增(WGD)。

随访分析则表明,这些WGD事件通常发生在癌症发展过程的相对早期,在某些谱系或癌症亚型的肿瘤中有更高的发生频率。

肿瘤基因组的倍性变化是人类癌症的标志。四倍体化 :一整套二倍体染色体的倍增,是由全基因组倍增(WGD)引起的一类倍性异常。在正常的人类发育中,基因组的四倍体化是罕见的,除了减数分裂过程中的生殖细胞。

在先前的研究中,WGD被认为是由细胞分裂中的潜在错误引起的。在人类肿瘤中,WGD偶然被鉴定为先前大规模DNA拷贝数改变(CNAs,copy-number alterations )的一部分或者是定义疾病进化的系统发育学。在实体瘤中研究WGD的一个挑战,是将单个WGD事件与可能是多个连续/独立的CNA区分开来。


Fig1:在肿瘤基因组中,等位基因(MCN,major copy number )的拷贝数应该在癌基因组的大部分区域升高。因此,作者对队列中所有患者的MCN为大于等于2的常染色体肿瘤基因组的量进行了量化,出现了一个双峰的结果,表明存在“两种不同的癌症”。

为了确认从杂交捕获结果推断的WGD,作者生成了匹配的整个外显子组测序数据,该肿瘤和该队列中149名患者的正常标本。 WGD在147例(99%)中是一致的,证实了研究者对靶向测序数据的WGD分析与推断的稳健性。

另外,因为WGD是从独立于体细胞突变数据的等位基因特异性拷贝数推断中调用的,作者使用突变等位基因部分来评估在WGD阳性基因组中调用的准确性,其中也存在WGD阴性的解决方案。


Fig. 3 | Genome doubling and outcome

作者研究了这两种相反的解决方案在受影响的基因组平衡四倍体区域中解释观察到的体细胞突变的突变等位基因部分的程度,并证实WGD阳性解决方案与对应于总共四个拷贝的一个和两个拷贝的突变等位基因部分一致。

总共有28.2%的癌症患者存在WGD。值得注意的是,这种WGD的速率类似于由癌症基因组图谱(TCGA)产生的6,184个原发未治疗肿瘤的全外显子组测序数据的第二正交组群(31%;参见方法)。在我们的队列中,WGD是人类癌症中最常见的分子异常之一,其流行率仅次于TP53突变(占受影响患者的39%)

WGD因肿瘤谱系和分子亚型而异。如图1c所示,58%的生殖系细胞肿瘤,以及5%的非霍奇金淋巴瘤和胃肠道神经内分泌肿瘤与WGD有关。 WGD还与组织学上不同的疾病亚型相关。

例如,乳头状甲状腺肿瘤中几乎没有WGD的证据。总之,通过常规免疫组织化学确认的110个具有MSI的肿瘤、并且用测序数据(补充图5)正交验证后发现,不存在WGD。

超过五分之一的野生型TP53肿瘤,特别是含有CCND1扩增或显示E2F介导的G1期阻滞的肿瘤。WGD是致癌KRAS突变和TERT启动子突变(每种约13%)的两倍多,这是另一个最常见的分子畸变。

研究人员解释说,WGD的患病率似乎因癌症亚型而异,并且具有不同的分子特征,促使我们对相关基因组改变、患者治疗情况进行更深入的研究。

在确定这9,692名前瞻性测序患者的癌症基因组中可能存在或不存在WGD后,作者系统地评估了其在常见和罕见癌症中的进化影响,基因组关联以及预后意义,并评估此类信息的可用性最终可能会对临床管理产生的影响。

“以WGD来鉴定原发性肿瘤的不良预后,例如文中描述的胰腺癌病例,可以为特定人群中的高风险患者设计新的辅助试验,”通讯作者,Barry Taylor(流行病学、肿瘤学家、生物统计学研究者)和他的同事指出“对来自癌症患者的正常配对标本同时进行测序至关重要。”

WGD是受影响癌症的宏观进化步骤,经历过WGD的肿瘤通过增加后续大规模单拷贝丢失的负担而进化出亚四倍体基因组。这些CNA在受影响病例的分子发病机制中出现,意味着WGD可能作为CNA亚克隆多样化的前体,最近已被证明与肺腺癌患者的不良预后相关。

事实上,我们在一些癌症类型的转移特异性中观察到的WGD患病率增加,而不是在这些肿瘤的进化后期出现并导致向转移性疾病的转变,这可能反映了早期事件,如果存在,表示原发性疾病的更具侵略性的子集,预后较差(如前列腺癌和胰腺癌)。

癌症类型中WGD的可变性可部分解释为癌细胞增殖率。 WGD预测癌症类型的发病率增加,包括KRAS突变结肠直肠癌和雌激素受体阳性乳腺癌,与既定的临床预后因素无关。我们得出结论,WGD在癌症中非常常见,并且是与癌症类型预后不良相关的宏观进化事件。

原始出处:Craig M. Bielski, Ahmet Zehir, Alexander V. Penson, et al. Genome doubling shapes the evolution and prognosis of advanced cancers. Nature Genetics (2018)

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  7. 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createdName=liye789132251, createdTime=Sat Jun 22 11:10:00 CST 2019, time=2019-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2006435, encodeId=dd3b200643583, content=<a href='/topic/show?id=924a3264381' target=_blank style='color:#2F92EE;'>#前瞻性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32643, encryptionId=924a3264381, topicName=前瞻性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5cb32500112, createdName=1508842480_96220437, createdTime=Thu Jun 27 03:10:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686227, encodeId=8036168622e6d, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 17 18:10:00 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948487, encodeId=a588194848e2a, content=<a href='/topic/show?id=8d388313290' target=_blank style='color:#2F92EE;'>#肿瘤靶向#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83132, encryptionId=8d388313290, topicName=肿瘤靶向)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=66962500501, createdName=yige2004, createdTime=Tue Oct 23 16:10:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066058, encodeId=4e4220660584a, content=<a href='/topic/show?id=47e99992319' target=_blank style='color:#2F92EE;'>#靶向测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99923, encryptionId=47e99992319, topicName=靶向测序)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Mon Oct 15 04:10:00 CST 2018, time=2018-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734028, encodeId=d0891e340287f, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Jan 03 21:10:00 CST 2019, time=2019-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546494, encodeId=156c154649452, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Thu Jul 19 07:10:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332410, encodeId=7b673324108e, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Wed Jul 18 09:26:31 CST 2018, time=2018-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332253, encodeId=2c38332253a1, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Jul 17 16:27:33 CST 2018, time=2018-07-17, status=1, ipAttribution=)]
    2019-01-03 canlab
  8. [GetPortalCommentsPageByObjectIdResponse(id=2049059, encodeId=83df204905976, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed Mar 27 20:10:00 CST 2019, time=2019-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883188, encodeId=bcde1883188b5, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jun 22 11:10:00 CST 2019, time=2019-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2006435, encodeId=dd3b200643583, content=<a href='/topic/show?id=924a3264381' target=_blank style='color:#2F92EE;'>#前瞻性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32643, encryptionId=924a3264381, topicName=前瞻性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5cb32500112, createdName=1508842480_96220437, createdTime=Thu Jun 27 03:10:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686227, encodeId=8036168622e6d, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 17 18:10:00 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948487, encodeId=a588194848e2a, content=<a href='/topic/show?id=8d388313290' target=_blank style='color:#2F92EE;'>#肿瘤靶向#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83132, encryptionId=8d388313290, topicName=肿瘤靶向)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=66962500501, createdName=yige2004, createdTime=Tue Oct 23 16:10:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066058, encodeId=4e4220660584a, content=<a href='/topic/show?id=47e99992319' target=_blank style='color:#2F92EE;'>#靶向测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99923, encryptionId=47e99992319, topicName=靶向测序)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Mon Oct 15 04:10:00 CST 2018, time=2018-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734028, encodeId=d0891e340287f, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Jan 03 21:10:00 CST 2019, time=2019-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546494, encodeId=156c154649452, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Thu Jul 19 07:10:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332410, encodeId=7b673324108e, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Wed Jul 18 09:26:31 CST 2018, time=2018-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332253, encodeId=2c38332253a1, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Jul 17 16:27:33 CST 2018, time=2018-07-17, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=2049059, encodeId=83df204905976, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed Mar 27 20:10:00 CST 2019, time=2019-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883188, encodeId=bcde1883188b5, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jun 22 11:10:00 CST 2019, time=2019-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2006435, encodeId=dd3b200643583, content=<a href='/topic/show?id=924a3264381' target=_blank style='color:#2F92EE;'>#前瞻性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32643, encryptionId=924a3264381, topicName=前瞻性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5cb32500112, createdName=1508842480_96220437, createdTime=Thu Jun 27 03:10:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686227, encodeId=8036168622e6d, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 17 18:10:00 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948487, encodeId=a588194848e2a, content=<a href='/topic/show?id=8d388313290' target=_blank style='color:#2F92EE;'>#肿瘤靶向#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83132, encryptionId=8d388313290, topicName=肿瘤靶向)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=66962500501, createdName=yige2004, createdTime=Tue Oct 23 16:10:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066058, encodeId=4e4220660584a, content=<a href='/topic/show?id=47e99992319' target=_blank style='color:#2F92EE;'>#靶向测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99923, encryptionId=47e99992319, topicName=靶向测序)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Mon Oct 15 04:10:00 CST 2018, time=2018-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734028, encodeId=d0891e340287f, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Jan 03 21:10:00 CST 2019, time=2019-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546494, encodeId=156c154649452, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Thu Jul 19 07:10:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332410, encodeId=7b673324108e, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Wed Jul 18 09:26:31 CST 2018, time=2018-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332253, encodeId=2c38332253a1, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Jul 17 16:27:33 CST 2018, time=2018-07-17, status=1, ipAttribution=)]
    2018-07-18 orangesking

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=2049059, encodeId=83df204905976, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed Mar 27 20:10:00 CST 2019, time=2019-03-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883188, encodeId=bcde1883188b5, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jun 22 11:10:00 CST 2019, time=2019-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2006435, encodeId=dd3b200643583, content=<a href='/topic/show?id=924a3264381' target=_blank style='color:#2F92EE;'>#前瞻性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32643, encryptionId=924a3264381, topicName=前瞻性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5cb32500112, createdName=1508842480_96220437, createdTime=Thu Jun 27 03:10:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1686227, encodeId=8036168622e6d, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri May 17 18:10:00 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948487, encodeId=a588194848e2a, content=<a href='/topic/show?id=8d388313290' target=_blank style='color:#2F92EE;'>#肿瘤靶向#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83132, encryptionId=8d388313290, topicName=肿瘤靶向)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=66962500501, createdName=yige2004, createdTime=Tue Oct 23 16:10:00 CST 2018, time=2018-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2066058, encodeId=4e4220660584a, content=<a href='/topic/show?id=47e99992319' target=_blank style='color:#2F92EE;'>#靶向测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99923, encryptionId=47e99992319, topicName=靶向测序)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Mon Oct 15 04:10:00 CST 2018, time=2018-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734028, encodeId=d0891e340287f, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Thu Jan 03 21:10:00 CST 2019, time=2019-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546494, encodeId=156c154649452, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Thu Jul 19 07:10:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332410, encodeId=7b673324108e, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Wed Jul 18 09:26:31 CST 2018, time=2018-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332253, encodeId=2c38332253a1, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Tue Jul 17 16:27:33 CST 2018, time=2018-07-17, status=1, ipAttribution=)]
    2018-07-17 1209e435m98(暂无昵称)

    学习了谢谢分享

    0

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