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    GENE DEFECTS AND MUTANT ALK KINASE IN HUMAN SOLID TUMORS
    9.
    发明申请
    GENE DEFECTS AND MUTANT ALK KINASE IN HUMAN SOLID TUMORS 审中-公开
    人类固体肿瘤中的基因缺陷和突变碱性激酶

    公开(公告)号：US20130209452A1

    公开(公告)日：2013-08-15

    申请号：US13618400

    申请日：2012-09-14

    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 ,  A61K31/713 ,  G01N33/68

    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： 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 been identified herein 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 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结合部分间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白，已经在人体实体肿瘤中被鉴定，例如， 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。

    Gene defects and mutant ALK kinase in human solid tumors
    10.
    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。