000119629 001__ 119629
000119629 005__ 20240228134945.0
000119629 0247_ $$2doi$$a10.1007/s00401-014-1337-4
000119629 0247_ $$2pmid$$apmid:25200321
000119629 0247_ $$2pmc$$apmc:PMC4201745
000119629 0247_ $$2ISSN$$a0001-6322
000119629 0247_ $$2ISSN$$a1432-0533
000119629 0247_ $$2altmetric$$aaltmetric:6116207
000119629 037__ $$aDKFZ-2017-00260
000119629 041__ $$aeng
000119629 082__ $$a610
000119629 1001_ $$aBechet, Denise$$b0
000119629 245__ $$aSpecific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas.
000119629 260__ $$aBerlin$$bSpringer$$c2014
000119629 3367_ $$2DRIVER$$aarticle
000119629 3367_ $$2DataCite$$aOutput Types/Journal article
000119629 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1520584999_4418
000119629 3367_ $$2BibTeX$$aARTICLE
000119629 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000119629 3367_ $$00$$2EndNote$$aJournal Article
000119629 520__ $$aStudies in pediatric high-grade astrocytomas (HGA) by our group and others have uncovered recurrent somatic mutations affecting highly conserved residues in histone 3 (H3) variants. One of these mutations leads to analogous p.Lys27Met (K27M) mutations in both H3.3 and H3.1 variants, is associated with rapid fatal outcome, and occurs specifically in HGA of the midline in children and young adults. This includes diffuse intrinsic pontine gliomas (80 %) and thalamic or spinal HGA (>90 %), which are surgically challenging locations with often limited tumor material available and critical need for specific histopathological markers. Here, we analyzed formalin-fixed paraffin-embedded tissues from 143 pediatric HGA and 297 other primary brain tumors or normal brain. Immunohistochemical staining for H3K27M was compared to tumor genotype, and also compared to H3 tri-methylated lysine 27 (H3K27me3) staining, previously shown to be drastically decreased in samples carrying this mutation. There was a 100 % concordance between genotype and immunohistochemical analysis of H3K27M in tumor samples. Mutant H3K27M was expressed in the majority of tumor cells, indicating limited intra-tumor heterogeneity for this specific mutation within the limits of our dataset. Both H3.1 and H3.3K27M mutants were recognized by this antibody while non-neoplastic elements, such as endothelial and vascular smooth muscle cells or lymphocytes, did not stain. H3K27me3 immunoreactivity was largely mutually exclusive with H3K27M positivity. These results demonstrate that mutant H3K27M can be specifically identified with high specificity and sensitivity using an H3K27M antibody and immunohistochemistry. Use of this antibody in the clinical setting will prove very useful for diagnosis, especially in the context of small biopsies in challenging midline tumors and will help orient care in the context of the extremely poor prognosis associated with this mutation.
000119629 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000119629 588__ $$aDataset connected to CrossRef, PubMed,
000119629 650_7 $$2NLM Chemicals$$aHistones
000119629 650_7 $$0AE28F7PNPL$$2NLM Chemicals$$aMethionine
000119629 7001_ $$aGielen, Gerrit G H$$b1
000119629 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b2$$udkfz
000119629 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b3$$udkfz
000119629 7001_ $$aRousso, Caterina$$b4
000119629 7001_ $$aFaury, Damien$$b5
000119629 7001_ $$aFiset, Pierre-Olivier$$b6
000119629 7001_ $$aBenlimane, Naciba$$b7
000119629 7001_ $$aLewis, Peter W$$b8
000119629 7001_ $$aLu, Chao$$b9
000119629 7001_ $$aDavid Allis, C.$$b10
000119629 7001_ $$aKieran, Mark W$$b11
000119629 7001_ $$aLigon, Keith L$$b12
000119629 7001_ $$aPietsch, Torsten$$b13
000119629 7001_ $$aEllezam, Benjamin$$b14
000119629 7001_ $$aAlbrecht, Steffen$$b15
000119629 7001_ $$aJabado, Nada$$b16
000119629 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-014-1337-4$$gVol. 128, no. 5, p. 733 - 741$$n5$$p733 - 741$$tActa neuropathologica$$v128$$x1432-0533$$y2014
000119629 909CO $$ooai:inrepo02.dkfz.de:119629$$pVDB
000119629 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000119629 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000119629 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000119629 9141_ $$y2014
000119629 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000119629 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bACTA NEUROPATHOL : 2015
000119629 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000119629 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000119629 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000119629 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000119629 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000119629 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000119629 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000119629 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000119629 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000119629 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000119629 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000119629 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bACTA NEUROPATHOL : 2015
000119629 9201_ $$0I:(DE-He78)G380-20160331$$kG380$$lKKE Neuropathologie$$x0
000119629 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x1
000119629 980__ $$ajournal
000119629 980__ $$aVDB
000119629 980__ $$aI:(DE-He78)G380-20160331
000119629 980__ $$aI:(DE-He78)B062-20160331
000119629 980__ $$aUNRESTRICTED