公开(公告)号：EP1507865A2

公开(公告)日：2005-02-23

申请号：EP03732512.3

申请日：2003-05-30

申请人： MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN ,  Netherland Cancer Institute

发明人： MISKEY, Csaba ,  IZSVAK, Zsuzsanna ,  IVICS, Zoltan ,  PLASTERK, Ronald

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N15/85 ,  A61K38/00 ,  C12N5/06 ,  A01K67/027

CPC分类号： C12N15/90 ,  C12N15/85 ,  C12N2800/60 ,  C12N2800/90 ,  C12N2840/44

摘要： The present invention relates to a transposon-based DNA integration system comprising (a) a transposon which is devoid of a polynucleotide encoding a functional transposase and which comprises a polynucleotide of interest, wherein the transposon comprises inverted repeats having a degree of identity with the repeats within SEQ ID NO: 2 and its inverted repeat, respectively, of at least 90%; and (b) a transposase having at its N-terminus a DNA binding domain comprising the sequences of SEQ ID NO: 3 and 4; or (c) a polynucleotide encoding the transposase of (b). The present invention further relates to a method of transferring a polynucleotide of interest into cells of a vertebrate comprising the step of introducing the transposon-based DNA integration system of the invention into said cells. In addition, the invention relates to a method of effecting RNAi comprising (a) stably introducing a transposon comprising an expression cassette expressing a short interfering RNA and a selectable marker gene as part of the trans poson-based DNA integration system of the invention into a cell; (b) selecting for cells expressing the selectable marker; and (c) assessing whether the transcription/translation of the desired gene is effected by RNAi. A further embodiment of the invention is a method of gene trapping genes comprising the steps of (a) introducing the transposon-based DNA integration system of the invention into a cell; and (b) assessing for the expression of a selectable marker wherein expression of a selectable marker is indicative of integration of the transposon into a transcibed gene of the cell.

公开(公告)号：EP2694678A2

公开(公告)日：2014-02-12

申请号：EP12716860.7

申请日：2012-04-04

申请人： Netherland Cancer Institute

发明人： BERNARDS, Rene ,  HUANG, Sidong ,  HOLZEL, Michael ,  BERNS, Katrien

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57415 ,  G01N33/57423 ,  G01N33/57496

摘要： The instant application provides methods and related compositions pertaining to the identification of resistance to anticancer treatment in. a patient. In a particular embodiment, the invention provides biomarkers for the identification of resistance to anticancer treatment in a breast cancer patient, wherein a reduced expression of a MEDIATOR and/or SWI/SNF complex gene in the breast cancer cells of the patient indicates that the breast cancer cells in the patient may be successfully treated with a ΡI3Κ and/or mTOR inhibitor.

公开(公告)号：EP1507865B1

公开(公告)日：2008-07-16

申请号：EP03732512.3

申请日：2003-05-30

申请人： MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN ,  Netherland Cancer Institute

发明人： MISKEY, Csaba ,  IZSVAK, Zsuzsanna ,  IVICS, Zoltan ,  PLASTERK, Ronald

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N15/85 ,  A61K38/00 ,  C12N5/06 ,  A01K67/027

CPC分类号： C12N15/90 ,  C12N15/85 ,  C12N2800/60 ,  C12N2800/90 ,  C12N2840/44

摘要： The present invention relates to a transposon-based DNA integration system comprising (a) a transposon which is devoid of a polynucleotide encoding a functional transposase and which comprises a polynucleotide of interest, wherein the transposon comprises inverted repeats having a degree of identity with the repeats within SEQ ID NO: 2 and its inverted repeat, respectively, of at least 90%; and (b) a transposase having at its N-terminus a DNA binding domain comprising the sequences of SEQ ID NO: 3 and 4; or (c) a polynucleotide encoding the transposase of (b). The present invention further relates to a method of transferring a polynucleotide of interest into cells of a vertebrate comprising the step of introducing the transposon-based DNA integration system of the invention into said cells. In addition, the invention relates to a method of effecting RNAi comprising (a) stably introducing a transposon comprising an expression cassette expressing a short interfering RNA and a selectable marker gene as part of the trans poson-based DNA integration system of the invention into a cell; (b) selecting for cells expressing the selectable marker; and (c) assessing whether the transcription/translation of the desired gene is effected by RNAi. A further embodiment of the invention is a method of gene trapping genes comprising the steps of (a) introducing the transposon-based DNA integration system of the invention into a cell; and (b) assessing for the expression of a selectable marker wherein expression of a selectable marker is indicative of integration of the transposon into a transcibed gene of the cell.

公开(公告)号：EP2694677A2

公开(公告)日：2014-02-12

申请号：EP12716857.3

申请日：2012-04-04

申请人： Netherland Cancer Institute

发明人： BERNARDS, Rene ,  HUANG, Sidong ,  HOLZEL, Michael

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158

摘要： The instant application provides methods and related compositions pertaining to the identification of resistance to anticancer treatment in a patient. In a particular embodiment, the invention provides biomarkers for the identification of resistance to anticancer treatment in a lung cancer patient, wherein a reduced expression of a MEDIATOR and/or SW1/SNF complex gene in the lung cancer cells of the patient indicates that the lung cancer cells in the patient may be resistant to treatment with a receptor tyrosine kinase inhibitor, such as gefitinib and/or erlotinib. In some embodiments, the invention relates to methods and related compositions for predicting resistance to anticancer treatment by detecting the expression levels of one or more TGF-beta pathway nucleic acids and/or proteins.