DE06814528T1 - Wiederkehrende genfusionen bei prostatakrebs - Google Patents
Wiederkehrende genfusionen bei prostatakrebs Download PDFInfo
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- DE06814528T1 DE06814528T1 DE6814528T DE06814528T DE06814528T1 DE 06814528 T1 DE06814528 T1 DE 06814528T1 DE 6814528 T DE6814528 T DE 6814528T DE 06814528 T DE06814528 T DE 06814528T DE 06814528 T1 DE06814528 T1 DE 06814528T1
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Abstract
Ein Verfahren zur Diagnose von Prostata-Krebs bei einem Patienten, umfassend: (a) die Bereitstellung einer Patientenprobe; und (b) Detektion der Probe auf die Anwesenheit oder die Abwesenheit einer Genfusion umfassend einen 5'-Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einen 3'-Teil von einem Gen eines ETS-Familienmitglieds, wobei die Anwesenheit der Genfusion in der Probe auf Prostata-Krebs bei dem Patienten hinweist.
Claims (41)
- Ein Verfahren zur Diagnose von Prostata-Krebs bei einem Patienten, umfassend: (a) die Bereitstellung einer Patientenprobe; und (b) Detektion der Probe auf die Anwesenheit oder die Abwesenheit einer Genfusion umfassend einen 5'-Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einen 3'-Teil von einem Gen eines ETS-Familienmitglieds, wobei die Anwesenheit der Genfusion in der Probe auf Prostata-Krebs bei dem Patienten hinweist.
- Das Verfahren nach Anspruch 1, wobei das Androgen-regulierte Gen ausgewählt ist aus der Gruppe bestehend aus TMPRSS2 und PSA.
- Das Verfahren nach Anspruch 2, wobei die transkriptionsregulatorische Region des Androgen-regulierten Gens eine Promotorregion des Androgen-regulierten Gens umfasst.
- Das Verfahren nach Anspruch 3, wobei die Promotorregion des Androgen-regulierten Gens ein Androgen-responsibles Element (ARE) des Androgen-regulierten Gens umfasst.
- Das Verfahren nach Anspruch 1, wobei das Gen des ETS-Familienmitglieds ausgewählt ist aus der Gruppe bestehend aus ERG, ETV1 (ER81), FLI1, ETS1, ETS2, ELK1, ETV6 (TEL1), ETV7 (TEL2), GABPα, ELF1, ETV4 (E1AF; PEA3), ETV5 (ERM), ERF, PEA3/E1AF, PU.1, ESE1/ESX, SAP1 (ELK4), ETV3 (METS), EWS/FLI1, ESE1, ESE2 (ELF5), ESE3, PDEF, NET (ELK3; SAP2), NERF (ELF2) und FEV.
- Das Verfahren nach Anspruch 1, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS umfassend einen 5'-Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einen 3'-Teil von einem Gen eines ETS-Familienmitglieds umfasst.
- Das Verfahren nach Anspruch 6, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS unter Anwendung von Nukleinsäuresequenzierungstechniken umfasst.
- Das Verfahren nach Anspruch 6, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS unter Anwendung von Nukleinsäurehybridisationstechniken umfasst.
- Das Verfahren nach Anspruch 8, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS unter Anwendung von Nukleinsäurehybridisationstechniken ausgewählt aus der Gruppe bestehend aus in situ Hybridisation (ISH), Mikroarray und Southern-Blot umfasst.
- Das Verfahren nach Anspruch 6, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS unter Anwendung eines Nukleinsäureamplifikationsverfahrens umfasst.
- Das Verfahren nach Anspruch 10, wobei der Schritt (b) die Detektion chromosomaler Umbauten genomischer DNS unter Anwendung eines Nukleinsäureamplifikationsverfahrens ausgewählt aus der Gruppe bestehend Polymerase-Kettenreaktion (PCR), Reverse Transkriptase-Polymerase-Kettenreaktion (RT-PCR), Transkriptions-Vermittelte Amplifikation (TMA), Ligase-Kettenreaktion (LCR), Strangdislokationsamplifikation (SDA) und Nukleinssäuresequenz-basierte Amplifikation (NASBA) umfasst.
- Das Verfahren nach Anspruch 1, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte umfassend einen 5'-Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einen 3'-Teil von einem Gen eines ETS-Familienmitglieds umfasst.
- Das Verfahren nach Anspruch 12, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte unter Anwendung einer Nukleinsäuresequenzierungstechnik umfasst.
- Das Verfahren nach Anspruch 12, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte unter Anwendung einer Nukleinsäurehybridisationstechnik umfasst.
- Das Verfahren nach Anspruch 14, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte unter Anwendung einer Nukleinsäurehybridisationstechnik ausgewählt aus der Gruppe bestehend aus in situ Hybridisation (ISH), Mikroarray und Southern-Blot umfasst.
- Das Verfahren nach Anspruch 15, wobei die in situ Hybridisation Fluoreszenz-in situ-Hybridisation (FISH) unter Anwendung einer Sonde ausgewählt aus der Gruppe bestehend aus: RP11-372O17; RP11-137J13; RP11-692L4; RP11-476D17; PR11-32L6; RP11-752M23; RP11-1107H21; RP11-639A7; RP11-1077M21; RP11-121A5; RP11-120C17; PR11-814F13 und RR11-535H11 ist.
- Das Verfahren nach Anspruch 12, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte unter Anwendung eines Nukleinsäureamplifikationsverfahrens umfasst.
- Das Verfahren nach Anspruch 17, wobei der Schritt (b) die Detektion chimärer mRNA-Transkripte DNS unter Anwendung eines Nukleinsäureamplifikationsverfahrens ausgewählt aus der Gruppe bestehend Polymerase-Kettenreaktion (PCR), Reverse Transkriptase-Polymerase-Kettenreaktion (RT-PCR), Transkriptions-Vermittelte Amplifikation (TMA), Ligase-Kettenreaktion (LCR), Strangdislokationsamplifikation (SDA), und Nukleinssäuresequenz-basierte Amplifikation (NASBA) umfasst.
- Das Verfahren nach Anspruch 1, wobei der Schritt (b) die Detektion eines Amino-endständig verkürzten Proteins eines ETS-Familienmitglieds als Ergebnis einer Fusion einer transkriptionsregulatorischen Region einer Androgen-regulierten Region eines Androgen-regulierten Gens mit einem Gen eines ETS-Familienmitglieds umfasst.
- Das Verfahren nach Anspruch 1, wobei der Schritt (b) die Detektion eines chimären Proteins umfasst, welches einen Amino-endständigen Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einen Carboxy-endständigen Teil eines Gens von einem Eta-Familienmitglied aufweist.
- Das Verfahren nach Anspruch 19 oder 20, wobei der Schritt (b) die Detektion des Proteins unter Anwendung einer Proteinsequenzierungstechnik umfasst.
- Das Verfahren nach Anspruch 19 oder 20, wobei der Schritt (b) die Detektion des Proteins unter Anwendung eines Immuntests umfasst.
- Das Verfahren nach Anspruch 22, wobei der Schritt (b) die Detektion des Proteins unter Anwendung eines Immuntests ausgewählt aus der Gruppe bestehend aus Immunpräzipitation; Western-Blot; ELISA; Immunhistochemie; Immunzytochemie; Durchflusszytometrie; und Immun-PCR umfasst.
- Das Verfahren nach Anspruch 1, wobei die Probe ausgewählt ist aus der Gruppe bestehend aus Gewebe, Blut, Urin, Samen, Prostata-Sekreten und Prostata-Zellen.
- Das Verfahren nach Anspruch 1, wobei die Genfusion eine Fusion aus TMPRSS2 and ERG ist und wobei das Verfahren des Weiteren den Schritt der Charakterisierung der Prostata-Zellen basierend auf der Anwesenheit oder Abwesenheit einer genomischen Deletion in der Genfusion umfasst.
- Das Verfahren nach Anspruch 25, wobei dar Genumbau eine Deletion genomischer DNS zwischen dem TMPRSS2 and dem ERG Gen auf dem Chromosom 21 ist.
- Das Verfahren nach Anspruch 26, wobei die Deletion die Deletion von Exon 1 des ERG-Gens einschließt.
- Das Verfahren nach Anspruch 26, wobei die Deletion die Deletion von Exon 3 des TMPRSS2-Gens einschließt.
- Das Verfahren nach Anspruch 26, wobei zwischen 2,8 and 2,85 Megabasen genomischer DNS deletiert sind.
- Das Verfahren nach Anspruch 29, wobei die Deletion unter Anwendung eines FISH-Assays unter Verwendung mindestens einer Fluoreszenz-markierten Sonde ausgewählt aus der Gruppe bestehend aus dem BAC-Klon RP11-137J13 und dem BAC-Klon RP11-24A11 detektiert wird.
- Das Verfahren nach Anspruch 28, wobei die Deletion unter Anwendung der Polymerase-Kettenreaktion (PCR) detektiert wird.
- Das Verfahren nach Anspruch 31, wobei die PCR unter Verwendung eines Primers ausgewählt aus der Gruppe bestehend aus SEQ ID Nr. 55 – SEQ ID Nr. 58 durchgeführt wird.
- Das Verfahren nach Anspruch 26, wobei die Anwesenheit der Deletion auf Metastasen-bildenden Prostata-Krebs bei dem Patienten hinweist.
- Eine Zusammensetzung für die Diagnose von Prostata-Krebs bei einem Patienten umfassend mindestens Eines der folgenden: (a) eine markierte Sonde umfassend eine Sequenz, welche mit der Grenzzone, an der der 5'-Teil einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens mit dem 3'-Teil eines Gens von einem ETS-Familienmitglied fusioniert, hybridisiert; (b) einer erste markierte Sonde umfassend eine Sequenz, welche mit einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens hybridisiert und eine zweite markierte Sonde umfassend eine Sequenz, welche mit einem Gen eines ETS-Familienmitglieds hybridisiert; (c) ein erster Amplifikationsoligonukleotid umfassend eine Sequenz, welche mit einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens hybridisiert und ein zweiter Amplifikationsoligonukleotid umfassend eine Sequenz, welche mit einem Gen eines ETS-Familienmitglieds hybridisiert; (d) ein Antikörper, der gegen ein Amino-endständig verkürztes Protein eines ETS-Familienmitglieds gerichtet ist und das Ergebnis einer Fusion einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens mit einem Gen eines ETS-Familienmitglieds ist; und (e) ein Antikörper, der gegen ein chimäres Protein mit einem Amino-endständigen Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einem Carboxy-endständigen Teil von einem Gen eines ETS-Familienmitglieds gerichtet ist.
- Ein Verfahren für die Analyse von Prostata-Krebszellen auf eine Deletion von genomischer DNS als Hinweis auf einen Krebs-assoziierten Umbau, umfassend: (a) den Erwerb einer Testprobe der Prostata-Zellen; (b) die Analyse der Prostata-Zellprobe um das Expressionsniveau eines oder mehrerer Gene ausgewählt aus der Gruppe bestehend aus: ETS2; WRB; PCP4; und MX1 zu ermitteln; (c) den Vergleich der in Schritt b) ermittelten Expressionsniveaus mit dem Niveau in einer Kontrollprobe; und (d) die Feststellung, dass eine Deletion stattgefunden hat wenn das für das Gen in der Testprobe ermittelte Expressionsniveau geringer ist als das der Kontrollprobe.
- Ein Verfahren zur Behandlung von Prostata-Krebs bei einem Patienten umfassend: die Verabreichung eines Mittels an den Patienten, welches mindestens eine biologische Aktivität einer Genfusion mit einem 5'-Teil von einer transkriptionsregulatorischen Region eines Androgen-regulierten Gens und einem 3'-Teil von einem Gen eines ETS-Familienmitglieds inhibiert.
- Das Verfahren nach Anspruch 36, wobei das Androgen-regulierte Gen ausgewählt ist aus der Gruppe bestehend aus TMPRSS2 and PSA.
- Das Verfahren nach Anspruch 37, wobei die transkriptionsregulatorische Region des Androgen-regulierten Gens eine Promotorregion des Androgen-regulierten Gens umfasst.
- Das Verfahren nach Anspruch 38, wobei die Promotorregion des Androgen-regulierten Gens ein Androgen-responsibles Element des Androgen-regulierten Gens umfasst.
- Das Verfahren nach Anspruch 36, wobei das ETS-Familienmitgliedgen ausgewählt ist aus der Gruppe bestehend aus ERG, ETV1 (ER81), FLI1, ETS1, ETS2, ELK1, ETV6 (TEL1), ETV7 (TEL2), GABPα, ELF1, ETV4 (E1AF; PEA3), ETV5 (ERM), ERF, PEA3/E1AF, PU.1, ESE1/ESX, SAP1 (ELK4), ETV3 (METS), EWS/FLI1, ESE1, ESE2 (ELF5), ESE3, PDEF, NET (ELK3; SAP2), NERF (ELF2) und FEV.
- Das Verfahren nach Anspruch 36, wobei das Mittel ausgewählt ist aus der Gruppe bestehend aus einem kleinen Molekül/einer niedermolekularen Verbindung, einer siRNS, einer Antisense-Nukleinsäure und einem Antikörper.
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CA2622295C (en) | 2019-01-15 |
CA2814598A1 (en) | 2007-03-22 |
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US20120296070A1 (en) | 2012-11-22 |
EP1934363B1 (de) | 2013-03-20 |
WO2007033187A2 (en) | 2007-03-22 |
US20100257617A1 (en) | 2010-10-07 |
JP2009507492A (ja) | 2009-02-26 |
EP2612870A1 (de) | 2013-07-10 |
AU2006291054A1 (en) | 2007-03-22 |
CA2622295A1 (en) | 2007-03-22 |
US20160319369A1 (en) | 2016-11-03 |
IL190095A (en) | 2012-12-31 |
US8969527B2 (en) | 2015-03-03 |
US9745635B2 (en) | 2017-08-29 |
EP1934363A2 (de) | 2008-06-25 |
US20130040858A1 (en) | 2013-02-14 |
US20090208937A1 (en) | 2009-08-20 |
US8211645B2 (en) | 2012-07-03 |
US10190173B2 (en) | 2019-01-29 |
WO2007033187A3 (en) | 2008-02-21 |
US20120295809A1 (en) | 2012-11-22 |
IL190095A0 (en) | 2008-08-07 |
US8580509B2 (en) | 2013-11-12 |
JP5512125B2 (ja) | 2014-06-04 |
EP1934363A4 (de) | 2011-08-10 |
AU2006291054B2 (en) | 2011-10-13 |
US7718369B2 (en) | 2010-05-18 |
US10041123B2 (en) | 2018-08-07 |
US20070212702A1 (en) | 2007-09-13 |
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