000169155 001__ 169155
000169155 005__ 20240229133642.0
000169155 0247_ $$2doi$$a10.1200/JCO.20.02540
000169155 0247_ $$2pmid$$apmid:34110923
000169155 0247_ $$2ISSN$$a0732-183X
000169155 0247_ $$2ISSN$$a1527-7755
000169155 0247_ $$2altmetric$$aaltmetric:107555718
000169155 037__ $$aDKFZ-2021-01289
000169155 041__ $$aEnglish
000169155 082__ $$a610
000169155 1001_ $$0P:(DE-He78)fce464e68d8888e5e7be72b7a197bca7$$aSchmitt-Hoffner, Felix$$b0$$eFirst author$$udkfz
000169155 245__ $$aFOXR2 Stabilizes MYCN Protein and Identifies Non-MYCN-Amplified Neuroblastoma Patients With Unfavorable Outcome.
000169155 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2021
000169155 3367_ $$2DRIVER$$aarticle
000169155 3367_ $$2DataCite$$aOutput Types/Journal article
000169155 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1634566842_4000
000169155 3367_ $$2BibTeX$$aARTICLE
000169155 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000169155 3367_ $$00$$2EndNote$$aJournal Article
000169155 500__ $$a#EA:B062#LA:B062#/ 2021 Oct 10;39(29):3217-3228
000169155 520__ $$aClinical outcomes of patients with neuroblastoma range from spontaneous tumor regression to fatality. Hence, understanding the mechanisms that cause tumor progression is crucial for the treatment of patients. In this study, we show that FOXR2 activation identifies a subset of neuroblastoma tumors with unfavorable outcome and we investigate the mechanism how FOXR2 relates to poor outcome in patients.We analyzed three independent transcriptional data sets of in total 1030 primary neuroblastomas with full clinical annotation. We performed immunoprecipitation for FOXR2 and MYCN and silenced FOXR2 expression in two neuroblastoma cell lines to examine the effect on cellular processes, transcriptome, and MYCN protein levels. Tumor samples were analyzed for protein levels of FOXR2 and MYCN.In three combined neuroblastoma data sets, 9% of tumors show expression of FOXR2 but have low levels of MYCN mRNA. FOXR2 expression identifies a group of patients with unfavorable outcome, showing 10-year overall survival rates of 53%-59%, and proves to be an independent prognostic factor compared with established risk factors. Transcriptionally, FOXR2-expressing tumors are very similar to MYCN-amplified tumors, suggesting that they might share a common mechanism of tumor initiation. FOXR2 knockdown in FOXR2-expressing neuroblastoma cell lines resulted in cell cycle arrest, reduced cell growth, cell death, and reduced MYCN protein levels, all indicating that FOXR2 is essential for these tumors. Finally, we show that FOXR2 binds and stabilizes MYCN protein and MYCN protein levels are highly increased in FOXR2-expressing tumors, in several cases comparable with MYCN-amplified samples.The stabilization of MYCN by FOXR2 represents an alternative mechanism to MYCN amplification to increase MYCN protein levels. As such, FOXR2 expression identifies another subset of neuroblastoma patients with unfavorable clinical outcome.
000169155 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0
000169155 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de
000169155 7001_ $$0P:(DE-He78)6f3ac5e773e94ee6127aaba91db70b25$$avan Rijn, Sjoerd$$b1
000169155 7001_ $$0P:(DE-He78)cd8295952c28dc5b483b5ba9386a5669$$aToprak, Umut H$$b2$$udkfz
000169155 7001_ $$0P:(DE-He78)c865b84c0142dfa1def7dfeb70302918$$aMauermann, Monika$$b3$$udkfz
000169155 7001_ $$0P:(DE-He78)c5791cc5875e5a2a7f950b79f5912a4f$$aRosemann, Felix$$b4
000169155 7001_ $$0P:(DE-He78)a3d2e48d4d32d6b3952996020fe8d1b5$$aHeit-Mondrzyk, Anke$$b5$$udkfz
000169155 7001_ $$0P:(DE-He78)a8c698e0904394407c5261932915daa5$$aHübner, Jens-Martin$$b6$$udkfz
000169155 7001_ $$0P:(DE-He78)dd60ad1c45db7fcacc5be5238ad17e7d$$aCamgöz, Aylin$$b7$$udkfz
000169155 7001_ $$0P:(DE-He78)311fe8118b7563b455ba84e94fccb3a8$$aHartlieb, Sabine$$b8$$udkfz
000169155 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b9$$udkfz
000169155 7001_ $$0P:(DE-He78)a579ca2567736066534409e732b31c91$$aHenrich, Kai-Oliver$$b10$$udkfz
000169155 7001_ $$0P:(DE-He78)91f32735ee876c579d63c05a7f4778dd$$aWestermann, Frank$$b11$$udkfz
000169155 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b12$$eLast author$$udkfz
000169155 773__ $$0PERI:(DE-600)2005181-5$$a10.1200/JCO.20.02540$$gp. JCO.20.02540 -$$n29$$p3217-3228$$tJournal of clinical oncology$$v39$$x1527-7755$$y2021
000169155 909CO $$ooai:inrepo02.dkfz.de:169155$$pVDB
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)fce464e68d8888e5e7be72b7a197bca7$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)6f3ac5e773e94ee6127aaba91db70b25$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)cd8295952c28dc5b483b5ba9386a5669$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c865b84c0142dfa1def7dfeb70302918$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c5791cc5875e5a2a7f950b79f5912a4f$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a3d2e48d4d32d6b3952996020fe8d1b5$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a8c698e0904394407c5261932915daa5$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)dd60ad1c45db7fcacc5be5238ad17e7d$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)311fe8118b7563b455ba84e94fccb3a8$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a579ca2567736066534409e732b31c91$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)91f32735ee876c579d63c05a7f4778dd$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000169155 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000169155 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
000169155 9130_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0
000169155 9141_ $$y2021
000169155 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2021-01-28$$wger
000169155 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ CLIN ONCOL : 2019$$d2021-01-28
000169155 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bJ CLIN ONCOL : 2019$$d2021-01-28
000169155 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x0
000169155 9201_ $$0I:(DE-He78)HD01-20160331$$kHD01$$lDKTK HD zentral$$x1
000169155 9201_ $$0I:(DE-He78)B087-20160331$$kB087$$lB087 Neuroblastom Genomik$$x2
000169155 980__ $$ajournal
000169155 980__ $$aVDB
000169155 980__ $$aI:(DE-He78)B062-20160331
000169155 980__ $$aI:(DE-He78)HD01-20160331
000169155 980__ $$aI:(DE-He78)B087-20160331
000169155 980__ $$aUNRESTRICTED