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    Mutant ROS expression in human cancer
    3.
    发明授权
    Mutant ROS expression in human cancer 有权
    突变型ROS在人类癌症中的表达

    公开(公告)号：US09364477B2

    公开(公告)日：2016-06-14

    申请号：US13146705

    申请日：2010-02-12

    申请人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    发明人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04 ,  A61K31/506 ,  G01N33/574 ,  G01N33/547

    CPC分类号： A61K31/506 ,  A61K31/4545 ,  C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/6869 ,  C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57438 ,  G01N33/57484 ,  G01N2333/9121 ,  G01N2800/52

    摘要： The invention provides the identification of the presence of mutant ROS protein in human cancer. In some embodiments, the mutant ROS are FIG-ROS fusion proteins comprising part of the FIG protein fused to the kinase domain of the ROS kinase. In some embodiments, the mutant ROS is the overexpression of wild-type ROS in cancerous tissues (or tissues suspected of being cancerous) where, in normal tissue of that same tissue type, ROS is not expressed or is expressed at lower levels. The mutant ROS proteins of the invention are anticipated to drive the proliferation and survival of a subgroup of human cancers, particularly in cancers of the liver (including bile duct), pancreas, kidney, and testes. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS polypeptides (e.g., a FIG-ROS(S) fusion polypeptide), probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The identification of the mutant ROS polypeptides enables new methods for determining the presence of these mutant ROS polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

    摘要翻译： 本发明提供了人类癌症中突变型ROS蛋白的存在的鉴定。 在一些实施方案中，突变体ROS是包含与ROS激酶的激酶结构域融合的FIG蛋白的部分的FIG-ROS融合蛋白。 在一些实施方案中，突变体ROS是野生型ROS在癌组织（或怀疑是癌性的组织）中的过表达，其中在相同组织类型的正常组织中ROS不被表达或以较低水平表达。 预期本发明的突变体ROS蛋白质可以驱动人类癌症亚群的增殖和存活，特别是在肝脏（包括胆管），胰腺，肾脏和睾丸癌。 因此，本发明部分地提供了分离的多核苷酸和编码所公开的突变型ROS多肽的载体（例如，FIG-ROS（S）融合多肽），用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合的试剂 和截短的多肽。 鉴定突变体ROS多肽使得能够确定生物样品中这些突变型ROS多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法 ，其也由本发明提供。

    Mutant ROS Expression In Human Cancer
    4.
    发明申请
    Mutant ROS Expression In Human Cancer 有权
    人类癌症中突变型ROS表达

    公开(公告)号：US20110287445A1

    公开(公告)日：2011-11-24

    申请号：US13146705

    申请日：2010-02-12

    申请人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    发明人： Ting-Lei Gu ,  Meghan Ann Tucker ,  Herbert Haack ,  Katherine Eleanor Crosby ,  Victoria McGuinness Rimkunas

    IPC分类号： G01N33/573 ,  G01N33/566 ,  C07H21/04 ,  C07H21/00 ,  C07K2/00 ,  C12N9/12 ,  C07K16/40

    CPC分类号： A61K31/506 ,  A61K31/4545 ,  C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/6869 ,  C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57438 ,  G01N33/57484 ,  G01N2333/9121 ,  G01N2800/52

    摘要： The invention provides the identification of the presence of mutant ROS protein in human cancer. In some embodiments, the mutant ROS are FIG-ROS fusion proteins comprising part of the FIG protein fused to the kinase domain of the ROS kinase. In some embodiments, the mutant ROS is the overexpression of wild-type ROS in cancerous tissues (or tissues suspected of being cancerous) where, in normal tissue of that same tissue type, ROS is not expressed or is expressed at lower levels. The mutant ROS proteins of the invention are anticipated to drive the proliferation and survival of a subgroup of human cancers, particularly in cancers of the liver (including bile duct), pancreas, kidney, and testes. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS polypeptides (e.g., a FIG-ROS(S) fusion polypeptide), probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The identification of the mutant ROS polypeptides enables new methods for determining the presence of these mutant ROS polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

    摘要翻译： 本发明提供了人类癌症中突变型ROS蛋白的存在的鉴定。 在一些实施方案中，突变体ROS是包含与ROS激酶的激酶结构域融合的FIG蛋白的部分的FIG-ROS融合蛋白。 在一些实施方案中，突变体ROS是野生型ROS在癌组织（或怀疑是癌性的组织）中的过表达，其中在相同组织类型的正常组织中ROS不被表达或以较低水平表达。 预期本发明的突变体ROS蛋白质可以驱动人类癌症亚群的增殖和存活，特别是在肝脏（包括胆管），胰腺，肾脏和睾丸癌。 因此，本发明部分地提供了分离的多核苷酸和编码所公开的突变型ROS多肽的载体（例如，FIG-ROS（S）融合多肽），用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合的试剂 和截短的多肽。 鉴定突变体ROS多肽使得能够确定生物样品中这些突变型ROS多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法 ，其也由本发明提供。