000120027 001__ 120027
000120027 005__ 20240228135008.0
000120027 0247_ $$2doi$$a10.1038/ng.2950
000120027 0247_ $$2pmid$$apmid:24705250
000120027 0247_ $$2pmc$$apmc:PMC4282994
000120027 0247_ $$2ISSN$$a1061-4036
000120027 0247_ $$2ISSN$$a1546-1718
000120027 0247_ $$2altmetric$$aaltmetric:2264557
000120027 037__ $$aDKFZ-2017-00615
000120027 041__ $$aeng
000120027 082__ $$a570
000120027 1001_ $$aFontebasso, Adam M$$b0
000120027 245__ $$aRecurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.
000120027 260__ $$aNew York, NY$$bNature America$$c2014
000120027 3367_ $$2DRIVER$$aarticle
000120027 3367_ $$2DataCite$$aOutput Types/Journal article
000120027 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1490702300_15176
000120027 3367_ $$2BibTeX$$aARTICLE
000120027 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000120027 3367_ $$00$$2EndNote$$aJournal Article
000120027 520__ $$aPediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease.
000120027 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000120027 588__ $$aDataset connected to CrossRef, PubMed,
000120027 650_7 $$2NLM Chemicals$$aBone Morphogenetic Proteins
000120027 650_7 $$2NLM Chemicals$$aSmad Proteins
000120027 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aACVR1 protein, human
000120027 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aActivin Receptors, Type I
000120027 7001_ $$aPapillon-Cavanagh, Simon$$b1
000120027 7001_ $$aSchwartzentruber, Jeremy$$b2
000120027 7001_ $$aNikbakht, Hamid$$b3
000120027 7001_ $$aGerges, Noha$$b4
000120027 7001_ $$aFiset, Pierre-Olivier$$b5
000120027 7001_ $$aBechet, Denise$$b6
000120027 7001_ $$aFaury, Damien$$b7
000120027 7001_ $$aDe Jay, Nicolas$$b8
000120027 7001_ $$aRamkissoon, Lori A$$b9
000120027 7001_ $$aCorcoran, Aoife$$b10
000120027 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b11$$udkfz
000120027 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b12$$udkfz
000120027 7001_ $$0P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aJohann, Pascal$$b13$$udkfz
000120027 7001_ $$aTomita, Tadanori$$b14
000120027 7001_ $$aGoldman, Stewart$$b15
000120027 7001_ $$aNagib, Mahmoud$$b16
000120027 7001_ $$aBendel, Anne$$b17
000120027 7001_ $$aGoumnerova, Liliana$$b18
000120027 7001_ $$aBowers, Daniel C$$b19
000120027 7001_ $$aLeonard, Jeffrey R$$b20
000120027 7001_ $$aRubin, Joshua B$$b21
000120027 7001_ $$aAlden, Tord$$b22
000120027 7001_ $$aBrowd, Samuel$$b23
000120027 7001_ $$aGeyer, J Russell$$b24
000120027 7001_ $$aLeary, Sarah$$b25
000120027 7001_ $$aJallo, George$$b26
000120027 7001_ $$aCohen, Kenneth$$b27
000120027 7001_ $$aGupta, Nalin$$b28
000120027 7001_ $$aPrados, Michael D$$b29
000120027 7001_ $$aCarret, Anne-Sophie$$b30
000120027 7001_ $$aEllezam, Benjamin$$b31
000120027 7001_ $$aCrevier, Louis$$b32
000120027 7001_ $$aKlekner, Almos$$b33
000120027 7001_ $$aBognar, Laszlo$$b34
000120027 7001_ $$aHauser, Peter$$b35
000120027 7001_ $$aGarami, Miklos$$b36
000120027 7001_ $$aMyseros, John$$b37
000120027 7001_ $$aDong, Zhifeng$$b38
000120027 7001_ $$00000-0002-5568-6586$$aSiegel, Peter M$$b39
000120027 7001_ $$aMalkin, Hayley$$b40
000120027 7001_ $$aLigon, Azra H$$b41
000120027 7001_ $$aAlbrecht, Steffen$$b42
000120027 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b43$$udkfz
000120027 7001_ $$aLigon, Keith L$$b44
000120027 7001_ $$aMajewski, Jacek$$b45
000120027 7001_ $$aJabado, Nada$$b46
000120027 7001_ $$aKieran, Mark W$$b47
000120027 773__ $$0PERI:(DE-600)1494946-5$$a10.1038/ng.2950$$gVol. 46, no. 5, p. 462 - 466$$n5$$p462 - 466$$tNature genetics$$v46$$x1546-1718$$y2014
000120027 909CO $$ooai:inrepo02.dkfz.de:120027$$pVDB
000120027 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000120027 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000120027 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ
000120027 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b43$$kDKFZ
000120027 9131_ $$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$$x0
000120027 9141_ $$y2014
000120027 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000120027 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000120027 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000120027 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT GENET : 2015
000120027 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000120027 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000120027 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000120027 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000120027 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000120027 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000120027 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000120027 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000120027 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000120027 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bNAT GENET : 2015
000120027 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x0
000120027 980__ $$ajournal
000120027 980__ $$aVDB
000120027 980__ $$aI:(DE-He78)B062-20160331
000120027 980__ $$aUNRESTRICTED