Clin Cancer Res:对3334名晚期前列腺癌患者的循环肿瘤DNA进行基因组学分析确定了可靶向的BRCA变异和AR耐药机制

2021-02-27 AlexYang MedSci原创

综合基因组图谱(CGP)对于转移去势抗性前列腺癌(mCRPC)患者的价值越来越大。mCRPC往往会转移到骨骼,组织活检难以进行。最近,有研究人员假设无细胞循环肿瘤DNA(ctDNA)的CGP可以提供一

综合基因组图谱(CGP)对于转移去势抗性前列腺癌(mCRPC)患者的价值越来越大。mCRPC往往会转移到骨骼,组织活检难以进行。最近,有研究人员假设无细胞循环肿瘤DNA(ctDNA)的CGP可以提供一种微创的替代方法来检测可靶向的基因组变异,为临床治疗提供信息

研究人员使用来自3334名mCRPC患者的血浆(包括来自TRITON2/3的1674个筛查样本),评估了ctDNA中检测到的基因组变异情况,并评估了与基于组织的CGP的一致性。结果表明,3129名患者(94%)的ctDNA可检测到,ctDNA的中位数为7.5%;295名(8.8%)患者的BRCA1/2发生了突变。在一致性分析中,72/837名患者在组织中检测到BRCA1/2突变,其中67名(93%)也可通过ctDNA鉴定,包括100%的预测种系变异。另外,ctDNA中包含一些组织检测未发现的BRCA1/2改变,且ctDNA富含治疗耐药性变异,以及可能的克隆性造血突变(如ATM和CHEK2)。在940/2213名患者(42%)中,研究人员检测到潜在的AR耐药性变异,包括扩增、多克隆和复杂突变、重排和外显子8的新型缺失。

液体和组织活检中BRCA1和2检测的一致性

最后,研究人员指出,来自mCRPC患者的ctDNA的基因组分析重现了组织活检中检测到的基因组图谱,在检测BRCA1/2突变方面有很高的一致性,但ctDNA中能够检测到更多的获得性耐药变异。ctDNA的CGP是对组织CGP的有力的临床补充。

原始出处:

Hanna Tukachinsky , Russell W Madison , Jon H Chung et al. Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms. Clin Cancer Res. Feb 2021

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    2021-03-01 智智灵药
  8. [GetPortalCommentsPageByObjectIdResponse(id=1953547, encodeId=c2e5195354e7c, content=<a href='/topic/show?id=b3ec60803a2' target=_blank style='color:#2F92EE;'>#期前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60803, encryptionId=b3ec60803a2, topicName=期前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4723380, createdName=yangcx0915, createdTime=Mon Jun 21 19:55:20 CST 2021, time=2021-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1971362, encodeId=edc119e136234, content=<a href='/topic/show?id=ee288039ece' target=_blank style='color:#2F92EE;'>#耐药机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80397, encryptionId=ee288039ece, topicName=耐药机制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=263b421, createdName=zhaozuguo, createdTime=Fri Mar 19 07:55:20 CST 2021, time=2021-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342789, encodeId=8aa71342e8958, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Mon Mar 01 05:55:20 CST 2021, time=2021-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412800, encodeId=eeed14128009d, content=<a href='/topic/show?id=86cf59813ad' target=_blank style='color:#2F92EE;'>#晚期前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59813, encryptionId=86cf59813ad, topicName=晚期前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=776d2903072, createdName=zhyy89, createdTime=Mon Mar 01 05:55:20 CST 2021, time=2021-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1469729, encodeId=845c1469e29e3, content=<a href='/topic/show?id=09224182601' target=_blank style='color:#2F92EE;'>#基因组学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41826, encryptionId=09224182601, topicName=基因组学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0257060332, createdName=gwc385, createdTime=Mon Mar 01 05:55:20 CST 2021, time=2021-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484879, encodeId=a84f14848e9ce, content=<a href='/topic/show?id=35a050454a5' target=_blank style='color:#2F92EE;'>#循环肿瘤DNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50454, encryptionId=35a050454a5, topicName=循环肿瘤DNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ac107986109, createdName=ms1948154235210413, createdTime=Mon Mar 01 05:55:20 CST 2021, time=2021-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1594076, encodeId=9b9615940e681, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Mon Mar 01 05:55:20 CST 2021, time=2021-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039391, encodeId=0cc0103939119, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Sat Feb 27 17:55:20 CST 2021, time=2021-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040969, encodeId=4aa7104096961, content=前列腺癌相关研究,学习了,谢谢梅斯, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Feb 27 17:55:20 CST 2021, time=2021-02-27, status=1, ipAttribution=)]
    2021-02-27 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

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    2021-02-27 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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