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    METHODS AND MATERIALS FOR IDENTIFYING THE ORIGIN OF A CARCINOMA OF UNKNOWN PRIMARY ORIGIN
    8.
    发明申请
    METHODS AND MATERIALS FOR IDENTIFYING THE ORIGIN OF A CARCINOMA OF UNKNOWN PRIMARY ORIGIN 审中-公开
    鉴定原核生物原核生物的方法和材料

    公开(公告)号：US20170073758A1

    公开(公告)日：2017-03-16

    申请号：US14855719

    申请日：2015-09-16

    申请人： Janssen Diagnostics LLC

    发明人： Yixin Wang ,  Abhijt Mazumder ,  Dmitri Talantov ,  Timothy Jatkoe ,  Jonathan Baden

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/158 ,  C12Q2600/16

    摘要： The present invention provides a method of identifying origin of a metastasis of unknown origin by obtaining a sample containing metastatic cells; measuring Biomarkers associated with at least two different carcinomas; combining the data from the Biomarkers into a linear discrimination analysis where the linear discrimination analysis normalizes the Biomarkers against a reference; and imposes a cut-off which optimizes sensitivity and specificity of each Biomarker, weights the prevalence of the carcinomas and selects a tissue of origin determining origin based on highest probability determined by the linear discrimination analysis or determining that the carcinoma is not derived from a particular set of carcinomas; and optionally measuring Biomarkers specific for one or more additional different carcinoma, and repeating the steps for additional Biomarkers.

    摘要翻译： 本发明提供了通过获得含有转移细胞的样品来鉴定未知来源的转移起点的方法; 测量与至少两种不同癌相关的生物标志物; 将来自生物标志物的数据组合成线性鉴别分析，其中线性鉴别分析使生物标志物反对参考标准化; 并强加了一个优化每个生物标志物的灵敏度和特异性的切断点，重视癌症的流行，并且基于通过线性鉴别分析确定的最高概率来选择确定起源的组织，或者确定癌症不是从特定的 一套癌; 并且任选地测量对一种或多种另外的不同癌特异性的生物标志物，并重复其它生物标志物的步骤。

    HIGHLY SENSITIVE METHOD FOR DETECTING LOW FREQUENCY MUTATIONS
    9.
    发明申请
    HIGHLY SENSITIVE METHOD FOR DETECTING LOW FREQUENCY MUTATIONS 审中-公开
    用于检测低频突变的高灵敏度方法

    公开(公告)号：US20160130641A1

    公开(公告)日：2016-05-12

    申请号：US14375894

    申请日：2013-02-13

    申请人： Janssen Diagnostics, LLC

    发明人： Haiying Wang ,  Yuqiu Jiang ,  Yixin Wang

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6827 ,  C12Q1/6858 ,  C12Q2525/186 ,  C12Q2537/163

    摘要： The disclosed edge-blocker oligonucleotide based AS-NEPB-PCR method amplifies allele specific DNA (or RNA) while dramatically blocking amplification of wild type (WT) DNA (or RNA). The AS-NEPB-PCR design allows ready modification of an existing PCR reaction setup with an edge-blocker oligonucleotide together with an allele specific primer complementary to the mutant sequence to achieve allele specific amplification. The method simplifies assay optimization procedures and achieved sensitivity sufficient to detect a signal present at 0.1% level with close to 100% specificity, which is useful in detecting SNP or genetic mutations. The method was used to detect three different genetic mutations in cancer, in KRAS, BRAF, and EGFR, with three different types of modified edge-blocker oligonucleotides (phosphate, inverted dT and amino-C7). It was possible to detect one copy of mutant DNA in 1000-copy of normal DNA background of a heterogeneous sample, and was far more sensitive than the other blocking method.

    摘要翻译： 所公开的基于边缘阻断剂寡核苷酸的AS-NEPB-PCR方法扩增等位基因特异性DNA（或RNA），同时显着阻断野生型（WT）DNA（或RNA）的扩增。 AS-NEPB-PCR设计允许利用边界阻断剂寡核苷酸与等位基因特异性引物与突变序列互补的等位基因特异性引物即可修改现有PCR反应设置，以实现等位基因特异性扩增。 该方法简化了测定优化程序，并实现了足以检测0.1％水平的信号，具有接近100％的特异性的灵敏度，可用于检测SNP或遗传突变。 该方法用于检测癌症，KRAS，BRAF和EGFR中的三种不同基因突变，其中三种不同类型的修饰的边缘阻断剂寡核苷酸（磷酸盐，反向dT和氨基-C C7）。 可以在异质样品的正常DNA背景的1000拷贝中检测到一个拷贝的突变体DNA，并且比其他阻断方法更敏感。