000143513 001__ 143513
000143513 005__ 20240229112555.0
000143513 0247_ $$2doi$$a10.1038/s41467-019-09633-9
000143513 0247_ $$2pmid$$apmid:30967556
000143513 0247_ $$2pmc$$apmc:PMC6456501
000143513 0247_ $$2altmetric$$aaltmetric:58778611
000143513 037__ $$aDKFZ-2019-01097
000143513 041__ $$aeng
000143513 082__ $$a500
000143513 1001_ $$0P:(DE-He78)5120a331b1c28045c8ca6a8b1c73c95f$$aGröschel, Stefan$$b0$$eFirst author
000143513 245__ $$aDefective homologous recombination DNA repair as therapeutic target in advanced chordoma.
000143513 260__ $$a[London]$$bNature Publishing Group UK$$c2019
000143513 3367_ $$2DRIVER$$aarticle
000143513 3367_ $$2DataCite$$aOutput Types/Journal article
000143513 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1668599538_5814
000143513 3367_ $$2BibTeX$$aARTICLE
000143513 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000143513 3367_ $$00$$2EndNote$$aJournal Article
000143513 520__ $$aChordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (n = 11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.7% of samples and co-occurred with genomic instability. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, which is preferentially toxic to HR-incompetent cells, led to prolonged clinical benefit in a patient with refractory chordoma, and whole-genome analysis at progression revealed a PARP1 p.T910A mutation predicted to disrupt the autoinhibitory PARP1 helical domain. These findings uncover a therapeutic opportunity in chordoma that warrants further exploration, and provide insight into the mechanisms underlying PARP inhibitor resistance.
000143513 536__ $$0G:(DE-HGF)POF3-311$$a311 - Signalling pathways, cell and tumor biology (POF3-311)$$cPOF3-311$$fPOF III$$x0
000143513 588__ $$aDataset connected to CrossRef, PubMed,
000143513 7001_ $$0P:(DE-HGF)0$$aHübschmann, Daniel$$b1$$eFirst author
000143513 7001_ $$aRaimondi, Francesco$$b2
000143513 7001_ $$0P:(DE-He78)5ea1944c122bc098a81df27a05572719$$aHorak, Peter$$b3
000143513 7001_ $$0P:(DE-He78)13b64bdd8d9a2fdb2ab13cc480819130$$aWarsow, Gregor$$b4
000143513 7001_ $$0P:(DE-He78)a15aa7d740f286aad9d8139d515e866c$$aFröhlich, Martina$$b5
000143513 7001_ $$00000-0002-8753-8238$$aKlink, Barbara$$b6
000143513 7001_ $$0P:(DE-He78)faeda50a6b472b04206eb573f9894d21$$aGieldon, Laura$$b7
000143513 7001_ $$0P:(DE-He78)135e8c8d1dd1b66b8127c3d1e3a9b6a0$$aHutter, Barbara$$b8
000143513 7001_ $$0P:(DE-He78)e053817bc90becc8a8dd8250e677e773$$aKleinheinz, Kortine$$b9
000143513 7001_ $$0P:(DE-He78)ea098e4d78abeb63afaf8c25ec6d6d93$$aBonekamp, David$$b10
000143513 7001_ $$aMarschal, Oliver$$b11
000143513 7001_ $$0P:(DE-He78)97208bef945f0ab6bf33ed9925685de4$$aChudasama, Priya$$b12
000143513 7001_ $$0P:(DE-He78)07af613eea059030daaed3bde1fd1ce7$$aMika, Jagoda$$b13
000143513 7001_ $$aGroth, Marie$$b14
000143513 7001_ $$0P:(DE-He78)a8e85c1bd89741ab0c2a28032ba81359$$aUhrig, Sebastian$$b15
000143513 7001_ $$0P:(DE-He78)27e428a621a82fda81b0d5a1ccab3907$$aKrämer, Stephen$$b16
000143513 7001_ $$0P:(DE-He78)1464357f7ec5faf677a390a414e50c88$$aHeining, Christoph$$b17
000143513 7001_ $$0P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aHeilig, Christoph$$b18
000143513 7001_ $$0P:(DE-He78)29306fd3ae9f1a9839ed888ebc5c8074$$aRichter, Daniela$$b19
000143513 7001_ $$0P:(DE-He78)63ceb91f3d4f8750e9e1b4967d6aab75$$aReisinger, Eva$$b20
000143513 7001_ $$0P:(DE-He78)83906db1355a576371363a4b9f107d3d$$aPfütze, Katrin$$b21
000143513 7001_ $$0P:(DE-He78)78b6aa82148e60b4d91e3a37a6d3d9a0$$aEils, Roland$$b22
000143513 7001_ $$0P:(DE-He78)1efb774993effe7a66a6ffc1b1cf9ccb$$aWolf, Stephan$$b23
000143513 7001_ $$0P:(DE-He78)5bacb661d5d7c0220d8f996d980ad8de$$avon Kalle, Christof$$b24
000143513 7001_ $$0P:(DE-HGF)0$$aBrandts, Christian$$b25
000143513 7001_ $$0P:(DE-He78)2c1a21d1cf5fdc9e297512c9d1354250$$aScholl, Claudia$$b26
000143513 7001_ $$0P:(DE-HGF)0$$aWeichert, Wilko$$b27
000143513 7001_ $$aRichter, Stephan$$b28
000143513 7001_ $$0P:(DE-HGF)0$$aBauer, Sebastian$$b29
000143513 7001_ $$0P:(DE-HGF)0$$aPenzel, Roland$$b30
000143513 7001_ $$0P:(DE-HGF)0$$aSchröck, Evelin$$b31
000143513 7001_ $$0P:(DE-HGF)0$$aStenzinger, Albrecht$$b32
000143513 7001_ $$0P:(DE-He78)d8a0e60e5e095f3161ee0de3712409bc$$aSchlenk, Richard$$b33
000143513 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b34
000143513 7001_ $$00000-0002-1905-4717$$aRussell, Robert B$$b35
000143513 7001_ $$0P:(DE-He78)157277fe62f07df1732f9d126a51d1b9$$aGlimm, Hanno$$b36$$eLast author
000143513 7001_ $$0P:(DE-He78)f2a782242acf94a3114d75c45dc75b37$$aSchlesner, Matthias$$b37$$eLast author
000143513 7001_ $$0P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aFröhling, Stefan$$b38$$eLast author
000143513 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-019-09633-9$$gVol. 10, no. 1, p. 1635$$n1$$p1635$$tNature Communications$$v10$$x2041-1723$$y2019
000143513 909CO $$ooai:inrepo02.dkfz.de:143513$$pVDB
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5120a331b1c28045c8ca6a8b1c73c95f$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5ea1944c122bc098a81df27a05572719$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)13b64bdd8d9a2fdb2ab13cc480819130$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a15aa7d740f286aad9d8139d515e866c$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)faeda50a6b472b04206eb573f9894d21$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)135e8c8d1dd1b66b8127c3d1e3a9b6a0$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e053817bc90becc8a8dd8250e677e773$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ea098e4d78abeb63afaf8c25ec6d6d93$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)97208bef945f0ab6bf33ed9925685de4$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)07af613eea059030daaed3bde1fd1ce7$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a8e85c1bd89741ab0c2a28032ba81359$$aDeutsches Krebsforschungszentrum$$b15$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)27e428a621a82fda81b0d5a1ccab3907$$aDeutsches Krebsforschungszentrum$$b16$$kDKFZ
000143513 9101_ $$0I:(DE-HGF)0$$6P:(DE-He78)1464357f7ec5faf677a390a414e50c88$$aExternal Institute$$b17$$kExtern
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aDeutsches Krebsforschungszentrum$$b18$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)29306fd3ae9f1a9839ed888ebc5c8074$$aDeutsches Krebsforschungszentrum$$b19$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)63ceb91f3d4f8750e9e1b4967d6aab75$$aDeutsches Krebsforschungszentrum$$b20$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)83906db1355a576371363a4b9f107d3d$$aDeutsches Krebsforschungszentrum$$b21$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)78b6aa82148e60b4d91e3a37a6d3d9a0$$aDeutsches Krebsforschungszentrum$$b22$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)1efb774993effe7a66a6ffc1b1cf9ccb$$aDeutsches Krebsforschungszentrum$$b23$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5bacb661d5d7c0220d8f996d980ad8de$$aDeutsches Krebsforschungszentrum$$b24$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b25$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2c1a21d1cf5fdc9e297512c9d1354250$$aDeutsches Krebsforschungszentrum$$b26$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b27$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b29$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b30$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b31$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b32$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)d8a0e60e5e095f3161ee0de3712409bc$$aDeutsches Krebsforschungszentrum$$b33$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)fc949170377b58098e46141d95c72661$$aDeutsches Krebsforschungszentrum$$b34$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)157277fe62f07df1732f9d126a51d1b9$$aDeutsches Krebsforschungszentrum$$b36$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f2a782242acf94a3114d75c45dc75b37$$aDeutsches Krebsforschungszentrum$$b37$$kDKFZ
000143513 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aDeutsches Krebsforschungszentrum$$b38$$kDKFZ
000143513 9131_ $$0G:(DE-HGF)POF3-311$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vSignalling pathways, cell and tumor biology$$x0
000143513 9141_ $$y2019
000143513 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2017
000143513 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000143513 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000143513 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000143513 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000143513 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000143513 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000143513 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review
000143513 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000143513 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000143513 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000143513 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000143513 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000143513 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences
000143513 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000143513 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000143513 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000143513 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000143513 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bNAT COMMUN : 2017
000143513 9201_ $$0I:(DE-He78)A380-20160331$$kA380$$lNWG Molekulare Leukämogenese$$x0
000143513 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x1
000143513 9201_ $$0I:(DE-He78)B080-20160331$$kB080$$lTheoretische Bioinformatik$$x2
000143513 9201_ $$0I:(DE-He78)A010-20160331$$kA010$$lA010 Stammzellen und Krebs$$x3
000143513 9201_ $$0I:(DE-He78)B340-20160331$$kB340$$lTranslationale Medizinische Onkologie$$x4
000143513 9201_ $$0I:(DE-He78)B240-20160331$$kB240$$lBioinformatik und Omics Data Analytics$$x5
000143513 9201_ $$0I:(DE-He78)B330-20160331$$kB330$$lAngewandte Bioinformatik$$x6
000143513 9201_ $$0I:(DE-He78)E010-20160331$$kE010$$lE010 Radiologie$$x7
000143513 9201_ $$0I:(DE-He78)A360-20160331$$kA360$$lKKE Mol. Hämatologie/Onkologie$$x8
000143513 9201_ $$0I:(DE-He78)W190-20160331$$kW190$$lHochdurchsatz-Sequenzierung$$x9
000143513 9201_ $$0I:(DE-He78)B290-20160331$$kB290$$lAngewandte Funktionelle Genomik$$x10
000143513 9201_ $$0I:(DE-He78)L301-20160331$$kL301$$lDKTK Dresden$$x11
000143513 9201_ $$0I:(DE-He78)L501-20160331$$kL501$$lDKTK Frankfurt$$x12
000143513 9201_ $$0I:(DE-He78)L701-20160331$$kL701$$lDKTK München$$x13
000143513 9201_ $$0I:(DE-He78)L401-20160331$$kL401$$lDKTK Essen$$x14
000143513 980__ $$ajournal
000143513 980__ $$aVDB
000143513 980__ $$aI:(DE-He78)A380-20160331
000143513 980__ $$aI:(DE-He78)L101-20160331
000143513 980__ $$aI:(DE-He78)B080-20160331
000143513 980__ $$aI:(DE-He78)A010-20160331
000143513 980__ $$aI:(DE-He78)B340-20160331
000143513 980__ $$aI:(DE-He78)B240-20160331
000143513 980__ $$aI:(DE-He78)B330-20160331
000143513 980__ $$aI:(DE-He78)E010-20160331
000143513 980__ $$aI:(DE-He78)A360-20160331
000143513 980__ $$aI:(DE-He78)W190-20160331
000143513 980__ $$aI:(DE-He78)B290-20160331
000143513 980__ $$aI:(DE-He78)L301-20160331
000143513 980__ $$aI:(DE-He78)L501-20160331
000143513 980__ $$aI:(DE-He78)L701-20160331
000143513 980__ $$aI:(DE-He78)L401-20160331
000143513 980__ $$aUNRESTRICTED