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    Mutant ROS expression in human cancer
    1.
    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
    3.
    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。

    Gene Defects And Mutant ALK Kinase In Human Solid Tumors
    5.
    发明申请
    Gene Defects And Mutant ALK Kinase In Human Solid Tumors 有权
    人类实体肿瘤中的基因缺陷和突变ALK激酶

    公开(公告)号：US20110021546A1

    公开(公告)日：2011-01-27

    申请号：US12891987

    申请日：2010-09-28

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： A61K31/517 ,  C12N9/12 ,  C07K16/40 ,  C07K2/00 ,  C07H21/00 ,  G01N33/573 ,  C12Q1/68 ,  G01N33/566 ,  A61P35/00

    CPC分类号： C12Q1/6886 ,  A61K31/713 ,  A61K38/00 ,  C07K14/47 ,  C07K2319/00 ,  C12N9/12 ,  C12N9/1205 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Y207/10001 ,  G01N33/57423 ,  G01N33/57484 ,  G01N33/6893 ,  G01N2333/912 ,  G01N2333/9121

    摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase 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： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，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和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶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，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。

    Gene defects and mutant ALK kinase in human solid tumors
    6.
    发明申请
    Gene defects and mutant ALK kinase in human solid tumors 有权
    人类实体瘤中的基因缺陷和突变ALK激酶

    公开(公告)号：US20100240034A1

    公开(公告)日：2010-09-23

    申请号：US12589176

    申请日：2009-10-19

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12N5/02

    CPC分类号： G01N33/574 ,  A61K38/00 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57484 ,  G01N2333/9121 ,  Y10T436/117497

    摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase 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： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，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和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶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，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。

    Gene defects and mutant ALK kinase in human solid tumors
    7.
    发明授权
    Gene defects and mutant ALK kinase in human solid tumors 有权
    人类实体瘤中的基因缺陷和突变ALK激酶

    公开(公告)号：US08486645B2

    公开(公告)日：2013-07-16

    申请号：US13438218

    申请日：2012-04-03

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： G01N33/53 ,  G01N33/563 ,  C12Q1/48 ,  C12N9/12 ,  G01N35/08

    CPC分类号： G01N33/574 ,  A61K38/00 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57484 ,  G01N2333/9121 ,  Y10T436/117497

    摘要： Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant 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.

    摘要翻译： 涉及染色体2的新型基因缺失和易位导致融合蛋白的结合，其部分的间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白结合，已经在人类实体瘤中被鉴定。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变多肽的载体，用于检测其的探针，分离的突变多肽和用于检测融合和截短的多肽的试剂。 本发明还提供了用于确定生物样品中这些突变体多肽的存在的方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变多核苷酸或多肽特征的癌症进展抑制方法。

    GENE DEFECTS AND MUTANT ALK KINASE IN HUMAN SOLID TUMORS
    8.
    发明申请
    GENE DEFECTS AND MUTANT ALK KINASE IN HUMAN SOLID TUMORS 有权
    人类固体肿瘤中的基因缺陷和突变碱性激酶

    公开(公告)号：US20120288872A1

    公开(公告)日：2012-11-15

    申请号：US13438218

    申请日：2012-04-03

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： G01N33/574

    CPC分类号： G01N33/574 ,  A61K38/00 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57484 ,  G01N2333/9121 ,  Y10T436/117497

    摘要： Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant 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.

    摘要翻译： 涉及染色体2的新型基因缺失和易位导致融合蛋白的结合，其部分的间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白结合，已经在人类实体瘤中被鉴定。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变多肽的载体，用于检测其的探针，分离的突变多肽和用于检测融合和截短的多肽的试剂。 本发明还提供了用于确定生物样品中这些突变体多肽的存在的方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变多核苷酸或多肽特征的癌症进展抑制方法。

    Gene defects and mutant ALK kinase in human solid tumors
    9.
    发明授权
    Gene defects and mutant ALK kinase in human solid tumors 有权
    人类实体瘤中的基因缺陷和突变ALK激酶

    公开(公告)号：US08168383B2

    公开(公告)日：2012-05-01

    申请号：US12589176

    申请日：2009-10-19

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： C12Q1/68 ,  C12Q1/48 ,  C07H21/00 ,  C12N9/12

    CPC分类号： G01N33/574 ,  A61K38/00 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57484 ,  G01N2333/9121 ,  Y10T436/117497

    摘要： Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant 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.

    摘要翻译： 涉及染色体2的新型基因缺失和易位导致融合蛋白的结合，其部分的间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白结合，已经在人类实体瘤中被鉴定。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变多肽的载体，用于检测其的探针，分离的突变多肽和用于检测融合和截短的多肽的试剂。 本发明还提供了用于确定生物样品中这些突变体多肽的存在的方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变多核苷酸或多肽特征的癌症进展抑制方法。

    Gene Defects and Mutant ALK Kinase in Human Solid Tumors
    10.
    发明申请
    Gene Defects and Mutant ALK Kinase in Human Solid Tumors 有权
    人类实体肿瘤中的基因缺陷和突变ALK激酶

    公开(公告)号：US20100304382A1

    公开(公告)日：2010-12-02

    申请号：US12714457

    申请日：2010-02-27

    申请人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    发明人： Klarisa Rikova ,  Herbert Haack ,  Laura Sullivan ,  Ailan Guo ,  Anthony Possemato ,  Joan MacNeill ,  Ting-Lei Gu ,  Jian Yu

    IPC分类号： C12Q1/68 ,  C12N15/12 ,  C12N15/85 ,  C12N5/10 ,  C12P21/02 ,  C12N9/96 ,  C12N5/00

    CPC分类号： C12Q1/6886 ,  A61K31/713 ,  A61K38/00 ,  C07K14/47 ,  C07K2319/00 ,  C12N9/12 ,  C12N9/1205 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Y207/10001 ,  G01N33/57423 ,  G01N33/57484 ,  G01N33/6893 ,  G01N2333/912 ,  G01N2333/9121

    摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase 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： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，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和截短的多肽的试剂。 所公开的这种新融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶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，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。