公开(公告)号：US07999080B2

公开(公告)日：2011-08-16

申请号：US12309310

申请日：2007-07-13

Applicant: Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

Inventor： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC: C07K16/18

CPC classification number: C12Q1/485 ,  C07K16/18 ,  C07K16/40 ,  C07K16/44 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

Abstract: The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

Abstract translation: 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20110045603A1

公开(公告)日：2011-02-24

申请号：US12763886

申请日：2010-04-20

Applicant: Ailan Guo ,  Albrecht Moritz ,  Anthony Possemato ,  Ting-Lei Gu ,  Jian Yu ,  Charles Lawrence Farnsworth ,  Corinne Michaud ,  Hong Ren ,  Jessica Ann Cherry ,  Jing Zhou ,  Valerie Lee Goss ,  Erik Spek ,  Yu Li ,  Meghan Ann Tucker ,  John Edward Rush, II ,  Matthew Stokes ,  Klarisa Rikova

Inventor： Ailan Guo ,  Albrecht Moritz ,  Anthony Possemato ,  Ting-Lei Gu ,  Jian Yu ,  Charles Lawrence Farnsworth ,  Corinne Michaud ,  Hong Ren ,  Jessica Ann Cherry ,  Jing Zhou ,  Valerie Lee Goss ,  Erik Spek ,  Yu Li ,  Meghan Ann Tucker ,  John Edward Rush, II ,  Matthew Stokes ,  Klarisa Rikova

IPC: G01N33/53 ,  C07K16/18

CPC classification number: C07K16/18 ,  C07K14/47 ,  C07K16/44 ,  G01N33/6842

Abstract: The invention discloses 990 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

Abstract translation: 本发明公开了在癌和白血病中鉴定的990个新的磷酸化位点，包含本发明的磷酸化位点的肽（包括AQUA肽），特异性结合本发明的新的磷酸化位点的抗体，以及上述的诊断和治疗用途。

公开(公告)号：US20110021546A1

公开(公告)日：2011-01-27

申请号：US12891987

申请日：2010-09-28

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

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

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

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20100240034A1

公开(公告)日：2010-09-23

申请号：US12589176

申请日：2009-10-19

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

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

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

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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20100009463A1

公开(公告)日：2010-01-14

申请号：US12309313

申请日：2007-07-13

Applicant: Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

Inventor： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

IPC: G01N33/566 ,  C07K16/18 ,  C07K14/47 ,  C12N5/16 ,  C12N5/18

CPC classification number: G01N33/57426 ,  C07B59/008 ,  C07K14/47 ,  C07K16/44 ,  G01N33/6842 ,  G01N2458/15

Abstract: The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

Abstract translation: 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20090263832A1

公开(公告)日：2009-10-22

申请号：US12086609

申请日：2006-11-29

Applicant: Roberto Polakiewicz ,  Ting-Lei Gu ,  Valerie Goss ,  Kimberly Lee

Inventor： Roberto Polakiewicz ,  Ting-Lei Gu ,  Valerie Goss ,  Kimberly Lee

IPC: G01N33/573 ,  C12Q1/48 ,  C07K16/18 ,  C12N5/16 ,  C12N5/18

CPC classification number: G01N33/57426

Abstract: The invention discloses nearly 123 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: protein kinases, adaptor/scaffold proteins, phosphatase/phospholipases, G proteins/GTPase activating proteins/guanine nucleotide exchange factors, cellular metabolism enzymes, DNA binding proteins, cytoskeletal proteins, cell cycle regulation proteins, proteases, RNA binding proteins, transcription proteins, translation initiation complex proteins, transferases, ubiquitin conjugating system proteins, vesicle proteins, actin binding proteins, apoptosis proteins, chemokine proteins, enzyme proteins extra cellular matrix proteins, helicases, hydrolases, immunoglobin superfamily proteins, inhibitor proteins, isomerases, ligases, lipid binding proteins, methyltransferases, motor proteins, receptor proteins, and chaperone proteins.

Abstract translation: 本发明公开了在信号转导蛋白中识别的近123个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白，如 以及使用试剂用于此目的的方法。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：蛋白激酶，衔接子/支架蛋白，磷酸酶/磷脂酶，G蛋白/ GTPase激活蛋白/鸟嘌呤核苷酸交换因子，细胞代谢酶，DNA结合蛋白，细胞骨架蛋白，细胞 循环调节蛋白，蛋白酶，RNA结合蛋白，转录蛋白，翻译起始复合蛋白​​，转移酶，泛素缀合系统蛋白，囊泡蛋白，肌动蛋白结合蛋白，凋亡蛋白，趋化因子蛋白，酶蛋白超细胞基质蛋白，解旋酶，水解酶，免疫球蛋白 超家族蛋白，抑制蛋白，异构酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，受体蛋白和伴侣蛋白。

公开(公告)号：US20090258436A1

公开(公告)日：2009-10-15

申请号：US12309310

申请日：2007-07-13

Applicant: Peter Hornbeck ,  Valerie Goss ,  Ting-Lei Gu ,  Albrecht Moritz ,  Kimberly Lee

Inventor： Peter Hornbeck ,  Valerie Goss ,  Ting-Lei Gu ,  Albrecht Moritz ,  Kimberly Lee

IPC: G01N33/566 ,  C07K16/18

CPC classification number: C12Q1/485 ,  C07K16/18 ,  C07K16/40 ,  C07K16/44 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

Abstract: The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

Abstract translation: 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。

公开(公告)号：US20090142777A1

公开(公告)日：2009-06-04

申请号：US11973019

申请日：2007-10-05

Applicant: Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee ,  Roberto Polakiewicz

Inventor： Valerie Goss ,  Albrecht Moritz ,  Ting-Lei Gu ,  Kimberly Lee ,  Roberto Polakiewicz

IPC: G01N33/573 ,  G01N33/566 ,  C07K16/18 ,  C07K14/00 ,  C12N5/06

CPC classification number: C07K16/3061 ,  C07K16/40

Abstract: The invention discloses 424 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.

Abstract translation: 本发明公开了在信号转导蛋白中鉴定的424个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质 作为使用试剂用于此目的的方法。 所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。

公开(公告)号：US20080014598A1

公开(公告)日：2008-01-17

申请号：US11744753

申请日：2007-05-04

Applicant: Thorsten Wiederhold ,  Valerie Goss ,  Albrecht Moritz ,  Klarisa Rikova ,  Ting-Lei Gu ,  Peter Hornbeck

Inventor： Thorsten Wiederhold ,  Valerie Goss ,  Albrecht Moritz ,  Klarisa Rikova ,  Ting-Lei Gu ,  Peter Hornbeck

IPC: G01N33/573 ,  C07K16/18 ,  C12N5/06

CPC classification number: C07K16/40 ,  C12Q1/485 ,  G01N33/6842 ,  G01N2333/91215

Abstract: The invention discloses ten newly discovered PI3K regulatory subunit phosphorylation sites, tyrosines 467, 452, 463, and 470 in PI3KR1 (PI3Kp85 alpha), tyrosines 464, 460, and 467 in PI3KR2 (PI3Kp85 beta), and tyrosines 199, 184, and 202 in PI3KR3 (PI3Kp55 gamma), and provides reagents, including polyclonal and monoclonal antibodies, that selectively bind to PI3K when phosphorylated at one of the disclosed sites. Also provided are assays utilizing this reagent, including methods for determining the phosphorylation of PI3K in a biological sample, selecting a patient suitable for PI3K inhibitor therapy, profiling PI3K activation in a test tissue, and identifying a compound that modulates phosphorylation of PI3K in a test tissue, by using a detectable reagent, such as the disclosed antibody, that binds to PI3K only when phosphorylated at a disclosed site. The sample or test tissue may be taken from a subject suspected of having cancer, such as lymphoma, glioma, and colon cancer, involving altered PI3K signaling.

Abstract translation: 本发明公开了PI3KR1（PI3Kp85α），PI3KR2（PI3Kp85β）中酪氨酸464,460和467和酪氨酸199,184和202中的10个新发现的PI3K调节亚基磷酸化位点，酪氨酸467,452,463和470 在PI3KR3（PI3Kp55γ）中，并且提供试剂，包括多克隆和单克隆抗体，当在所公开的位点之一磷酸化时选择性地结合PI3K。 还提供了使用该试剂的测定法，包括用于测定生物样品中PI3K的磷酸化的方法，选择适合于PI3K抑制剂治疗的患者，在测试组织中分析PI3K活化，以及鉴定在测试中调节PI3K磷酸化的化合物 组织，通过使用仅在所公开的位点磷酸化时与PI3K结合的可检测试剂，例如所公开的抗体。 样品或测试组织可以取自怀疑患有癌症的受试者，例如淋巴瘤，神经胶质瘤和结肠癌，涉及改变的PI3K信号传导。

公开(公告)号：US08486645B2

公开(公告)日：2013-07-16

申请号：US13438218

申请日：2012-04-03

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

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

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

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

Abstract: 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.

Abstract translation: 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。