000277810 001__ 277810
000277810 005__ 20240229155025.0
000277810 0247_ $$2doi$$a10.1038/s41467-023-40235-8
000277810 0247_ $$2pmid$$apmid:37500667
000277810 0247_ $$2altmetric$$aaltmetric:152065718
000277810 037__ $$aDKFZ-2023-01521
000277810 041__ $$aEnglish
000277810 082__ $$a500
000277810 1001_ $$0P:(DE-He78)a5e60710c7515b3e1de74ced6928a9dd$$aSigaud, Romain$$b0$$eFirst author$$udkfz
000277810 245__ $$aMAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.
000277810 260__ $$a[London]$$bNature Publishing Group UK$$c2023
000277810 3367_ $$2DRIVER$$aarticle
000277810 3367_ $$2DataCite$$aOutput Types/Journal article
000277810 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1690550187_11049
000277810 3367_ $$2BibTeX$$aARTICLE
000277810 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000277810 3367_ $$00$$2EndNote$$aJournal Article
000277810 500__ $$a#EA:B310#LA:B310#
000277810 520__ $$aPediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent PDX dataset. The MSSs discern gliomas with varying MAPK alterations and are higher in pLGG compared to other pediatric CNS tumors. Heterogenous MSSs within pLGGs with the same MAPK alteration identify proportions of potentially sensitive patients. The MEKi MSS predicts treatment response in a small set of pLGG patients treated with trametinib. High MSSs correlate with a higher immune cell infiltration, with high expression in the microglia compartment in single-cell RNA sequencing data, while low MSSs correlate with low immune infiltration and increased neuronal score. The MSSs represent predictive tools for the stratification of pLGG patients and should be prospectively validated in clinical trials. Our data supports a role for microglia in the response to MAPKi.
000277810 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0
000277810 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000277810 7001_ $$00000-0002-2488-0706$$aAlbert, Thomas K$$b1
000277810 7001_ $$00009-0001-7436-5067$$aHess, Caroline$$b2
000277810 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b3$$udkfz
000277810 7001_ $$0P:(DE-He78)4eea644f475edc544c770c6842820c71$$aWinkler, Nadine$$b4$$udkfz
000277810 7001_ $$0P:(DE-He78)4679059a19b1f3cd341bd27d0ddb7c45$$aKocher, Daniela$$b5$$udkfz
000277810 7001_ $$aWalter, Carolin$$b6
000277810 7001_ $$00000-0001-8823-0238$$aMünter, Daniel$$b7
000277810 7001_ $$0P:(DE-He78)a23e88cc676489fe05be8c178ceaf58e$$aSelt, Florian$$b8$$udkfz
000277810 7001_ $$0P:(DE-He78)7d5cd95cbedad26188a1df9eeca335ef$$aUsta, Diren$$b9$$udkfz
000277810 7001_ $$0P:(DE-He78)3de637452ba900e2bdd359b8f41953bf$$aEcker, Jonas$$b10$$udkfz
000277810 7001_ $$aBrentrup, Angela$$b11
000277810 7001_ $$aHasselblatt, Martin$$b12
000277810 7001_ $$00000-0002-6642-7774$$aThomas, Christian$$b13
000277810 7001_ $$aVarghese, Julian$$b14
000277810 7001_ $$aCapper, David$$b15
000277810 7001_ $$aThomale, Ulrich W$$b16
000277810 7001_ $$00000-0003-3135-3872$$aHernáiz Driever, Pablo$$b17
000277810 7001_ $$00000-0001-9094-3632$$aSimon, Michèle$$b18
000277810 7001_ $$aHorn, Svea$$b19
000277810 7001_ $$aHerz, Nina Annika$$b20
000277810 7001_ $$aKoch, Arend$$b21
000277810 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b22$$udkfz
000277810 7001_ $$0P:(DE-He78)875b52cddc351d6eca86de4f404f4631$$aHamelmann, Stefan$$b23$$udkfz
000277810 7001_ $$00000-0001-5866-0501$$aFaria-Andrade, Augusto$$b24
000277810 7001_ $$00000-0003-2485-3692$$aJabado, Nada$$b25
000277810 7001_ $$00000-0001-9843-7486$$aSchuhmann, Martin U$$b26
000277810 7001_ $$aSchouten-van Meeteren, Antoinette Y N$$b27
000277810 7001_ $$00000-0002-5587-0439$$aHoving, Eelco$$b28
000277810 7001_ $$0P:(DE-He78)492a2f9f2a95bcb0609e37d1ce1e13a9$$aBrummer, Tilman$$b29$$udkfz
000277810 7001_ $$0P:(DE-He78)a6b5fcabf661bef95109dbee87dc5271$$avan Tilburg, Cornelis Martinus$$b30$$udkfz
000277810 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b31$$udkfz
000277810 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b32$$udkfz
000277810 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b33$$udkfz
000277810 7001_ $$00000-0002-5676-8102$$aKerl, Kornelius$$b34
000277810 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b35$$eLast author$$udkfz
000277810 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-40235-8$$gVol. 14, no. 1, p. 4533$$n1$$p4533$$tNature Communications$$v14$$x2041-1723$$y2023
000277810 909CO $$ooai:inrepo02.dkfz.de:277810$$pVDB
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a5e60710c7515b3e1de74ced6928a9dd$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$60009-0001-7436-5067$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4eea644f475edc544c770c6842820c71$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4679059a19b1f3cd341bd27d0ddb7c45$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a23e88cc676489fe05be8c178ceaf58e$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7d5cd95cbedad26188a1df9eeca335ef$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3de637452ba900e2bdd359b8f41953bf$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aDeutsches Krebsforschungszentrum$$b22$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)875b52cddc351d6eca86de4f404f4631$$aDeutsches Krebsforschungszentrum$$b23$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)492a2f9f2a95bcb0609e37d1ce1e13a9$$aDeutsches Krebsforschungszentrum$$b29$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a6b5fcabf661bef95109dbee87dc5271$$aDeutsches Krebsforschungszentrum$$b30$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b31$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aDeutsches Krebsforschungszentrum$$b32$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b33$$kDKFZ
000277810 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aDeutsches Krebsforschungszentrum$$b35$$kDKFZ
000277810 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0
000277810 9141_ $$y2023
000277810 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2021-10-13T14:44:21Z
000277810 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2022-11-11
000277810 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-11
000277810 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-11
000277810 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2022-11-11
000277810 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2022-11-11
000277810 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2022$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-05-02T09:09:09Z
000277810 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-05-02T09:09:09Z
000277810 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review$$d2023-05-02T09:09:09Z
000277810 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2023-08-29
000277810 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bNAT COMMUN : 2022$$d2023-08-29
000277810 9202_ $$0I:(DE-He78)B310-20160331$$kB310$$lKKE Pädiatrische Onkologie$$x0
000277810 9200_ $$0I:(DE-He78)B310-20160331$$kB310$$lKKE Pädiatrische Onkologie$$x0
000277810 9201_ $$0I:(DE-He78)B310-20160331$$kB310$$lKKE Pädiatrische Onkologie$$x0
000277810 9201_ $$0I:(DE-He78)HD01-20160331$$kHD01$$lDKTK HD zentral$$x1
000277810 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lC060 Biostatistik$$x2
000277810 9201_ $$0I:(DE-He78)B300-20160331$$kB300$$lKKE Neuropathologie$$x3
000277810 9201_ $$0I:(DE-He78)FR01-20160331$$kFR01$$lDKTK Koordinierungsstelle Freiburg$$x4
000277810 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x5
000277810 9201_ $$0I:(DE-He78)B360-20160331$$kB360$$lPädiatische Gliomforschung$$x6
000277810 980__ $$ajournal
000277810 980__ $$aVDB
000277810 980__ $$aI:(DE-He78)B310-20160331
000277810 980__ $$aI:(DE-He78)HD01-20160331
000277810 980__ $$aI:(DE-He78)C060-20160331
000277810 980__ $$aI:(DE-He78)B300-20160331
000277810 980__ $$aI:(DE-He78)FR01-20160331
000277810 980__ $$aI:(DE-He78)B062-20160331
000277810 980__ $$aI:(DE-He78)B360-20160331
000277810 980__ $$aUNRESTRICTED