Show simple item record

dc.contributor.authorBechet, Deniseen_US
dc.contributor.authorGielen, Gerrit G. H.en_US
dc.contributor.authorKorshunov, Andreyen_US
dc.contributor.authorPfister, Stefan M.en_US
dc.contributor.authorRousso, Caterinaen_US
dc.contributor.authorFaury, Damienen_US
dc.contributor.authorFiset, Pierre-Olivieren_US
dc.contributor.authorBenlimane, Nacibaen_US
dc.contributor.authorLewis, Peter W.en_US
dc.contributor.authorLu, Chaoen_US
dc.contributor.authorDavid Allis, C.en_US
dc.contributor.authorKieran, Mark W.en_US
dc.contributor.authorLigon, Keith L.en_US
dc.contributor.authorPietsch, Torstenen_US
dc.contributor.authorEllezam, Benjaminen_US
dc.contributor.authorAlbrecht, Steffenen_US
dc.contributor.authorJabado, Nadaen_US
dc.date.accessioned2014-11-03T17:40:07Z
dc.date.issued2014en_US
dc.identifier.citationBechet, D., G. G. H. Gielen, A. Korshunov, S. M. Pfister, C. Rousso, D. Faury, P. Fiset, et al. 2014. “Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas.” Acta Neuropathologica 128 (5): 733-741. doi:10.1007/s00401-014-1337-4. http://dx.doi.org/10.1007/s00401-014-1337-4.en
dc.identifier.issn0001-6322en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347577
dc.description.abstractStudies 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. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1337-4) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherSpringer Berlin Heidelbergen
dc.relation.isversionofdoi:10.1007/s00401-014-1337-4en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201745/pdf/en
dash.licenseLAAen_US
dc.subjectK27Men
dc.subjectHistone 3 variantsen
dc.subjectIHCen
dc.subjectK27 trimethylationen
dc.subjectHigh-grade astrocytomasen
dc.titleSpecific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomasen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalActa Neuropathologicaen
dash.depositing.authorKieran, Mark W.en_US
dc.date.available2014-11-03T17:40:07Z
dc.identifier.doi10.1007/s00401-014-1337-4*
dash.authorsorderedfalse
dash.contributor.affiliatedKieran, Mark W.
dash.contributor.affiliatedLigon, Keith


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record