000141666 001__ 141666 000141666 005__ 20240229105127.0 000141666 0247_ $$2doi$$a10.1186/s40478-018-0614-1 000141666 0247_ $$2pmid$$apmid:30396367 000141666 0247_ $$2pmc$$apmc:PMC6219253 000141666 0247_ $$2altmetric$$aaltmetric:51128789 000141666 037__ $$aDKFZ-2018-01937 000141666 041__ $$aeng 000141666 082__ $$a610 000141666 1001_ $$aCastel, David$$b0 000141666 245__ $$aTranscriptomic and epigenetic profiling of diffuse midline gliomas, H3 K27M-mutant discriminate two subgroups based on the type of histone H3 mutated and not supratentorial or infratentorial location. 000141666 260__ $$aLondon$$bBiomed Central$$c2018 000141666 3367_ $$2DRIVER$$aarticle 000141666 3367_ $$2DataCite$$aOutput Types/Journal article 000141666 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1659604635_16656 000141666 3367_ $$2BibTeX$$aARTICLE 000141666 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000141666 3367_ $$00$$2EndNote$$aJournal Article 000141666 520__ $$aDiffuse midline glioma (DMG), H3 K27M-mutant, is a new entity in the updated WHO classification grouping together diffuse intrinsic pontine gliomas and infiltrating glial neoplasms of the midline harboring the same canonical mutation at the Lysine 27 of the histones H3 tail.Two hundred and fifteen patients younger than 18 years old with centrally-reviewed pediatric high-grade gliomas (pHGG) were included in this study. Comprehensive transcriptomic (n = 140) and methylation (n = 80) profiling was performed depending on the material available, in order to assess the biological uniqueness of this new entity compared to other midline and hemispheric pHGG.Tumor classification based on gene expression (GE) data highlighted the similarity of K27M DMG independently of their location along the midline. T-distributed Stochastic Neighbor Embedding (tSNE) analysis of methylation profiling confirms the discrimination of DMG from other well defined supratentorial tumor subgroups. Patients with diffuse intrinsic pontine gliomas (DIPG) and thalamic DMG exhibited a similarly poor prognosis (11.1 and 10.8 months median overall survival, respectively). Interestingly, H3.1-K27M and H3.3-K27M primary tumor samples could be distinguished based both on their GE and DNA methylation profiles, suggesting that they might arise from a different precursor or from a different epigenetic reorganization.These differences in DNA methylation profiles were conserved in glioma stem-like cell culture models of DIPG which mimicked their corresponding primary tumor. ChIP-seq profiling of H3K27me3 in these models indicate that H3.3-K27M mutated DIPG stem cells exhibit higher levels of H3K27 trimethylation which are correlated with fewer genes expressed by RNAseq. When considering the global distribution of the H3K27me3 mark, we observed that intergenic regions were more trimethylated in the H3.3-K27M mutated cells compared to the H3.1-K27M mutated ones.H3 K27M-mutant DMG represent a homogenous group of neoplasms compared to other pediatric gliomas that could be further separated based on the type of histone H3 variant mutated and their respective epigenetic landscapes. As these characteristics drive different phenotypes, these findings may have important implication for the design of future trials in these specific types of neoplasms. 000141666 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000141666 588__ $$aDataset connected to CrossRef, PubMed, 000141666 7001_ $$aPhilippe, Cathy$$b1 000141666 7001_ $$aKergrohen, Thomas$$b2 000141666 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b3$$udkfz 000141666 7001_ $$aMerlevede, Jane$$b4 000141666 7001_ $$aBarret, Emilie$$b5 000141666 7001_ $$aPuget, Stéphanie$$b6 000141666 7001_ $$aSainte-Rose, Christian$$b7 000141666 7001_ $$aKramm, Christof M$$b8 000141666 7001_ $$aJones, Chris$$b9 000141666 7001_ $$aVarlet, Pascale$$b10 000141666 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b11$$udkfz 000141666 7001_ $$aGrill, Jacques$$b12 000141666 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b13$$udkfz 000141666 7001_ $$00000-0002-8509-6165$$aDebily, Marie-Anne$$b14 000141666 773__ $$0PERI:(DE-600)2715589-4$$a10.1186/s40478-018-0614-1$$gVol. 6, no. 1, p. 117$$n1$$p117$$tActa Neuropathologica Communications$$v6$$x2051-5960$$y2018 000141666 909CO $$ooai:inrepo02.dkfz.de:141666$$pVDB 000141666 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000141666 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ 000141666 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ 000141666 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 000141666 9141_ $$y2018 000141666 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bACTA NEUROPATHOL COM : 2017 000141666 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000141666 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000141666 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000141666 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central 000141666 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000141666 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000141666 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review 000141666 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ 000141666 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000141666 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000141666 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000141666 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000141666 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000141666 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bACTA NEUROPATHOL COM : 2017 000141666 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x0 000141666 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x1 000141666 9201_ $$0I:(DE-He78)B360-20160331$$kB360$$lPediatric Glioma$$x2 000141666 980__ $$ajournal 000141666 980__ $$aVDB 000141666 980__ $$aI:(DE-He78)B062-20160331 000141666 980__ $$aI:(DE-He78)L101-20160331 000141666 980__ $$aI:(DE-He78)B360-20160331 000141666 980__ $$aUNRESTRICTED