Kramm, Christof M.

[["dc.bibliographiccitation.artnumber","117"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Castel, David"],["dc.contributor.author","Philippe, Cathy"],["dc.contributor.author","Kergrohen, Thomas"],["dc.contributor.author","Sill, Martin"],["dc.contributor.author","Merlevede, Jane"],["dc.contributor.author","Barret, Emilie"],["dc.contributor.author","Puget, Stéphanie"],["dc.contributor.author","Sainte-Rose, Christian"],["dc.contributor.author","Kramm, Christof M."],["dc.contributor.author","Jones, Chris"],["dc.contributor.author","Varlet, Pascale"],["dc.contributor.author","Pfister, Stefan M."],["dc.contributor.author","Grill, Jacques"],["dc.contributor.author","Jones, David T. W."],["dc.contributor.author","Debily, Marie-Anne"],["dc.date.accessioned","2019-07-09T11:51:10Z"],["dc.date.available","2019-07-09T11:51:10Z"],["dc.date.issued","2018"],["dc.description.abstract","Diffuse 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."],["dc.identifier.doi","10.1186/s40478-018-0614-1"],["dc.identifier.pmid","30396367"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16062"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59888"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Transcriptomic 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"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","78"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Andreiuolo, Felipe"],["dc.contributor.author","Lisner, Tomo"],["dc.contributor.author","Zlocha, Jozef"],["dc.contributor.author","Kramm, Christof"],["dc.contributor.author","Koch, Arend"],["dc.contributor.author","Bison, Brigitte"],["dc.contributor.author","Gareton, Albane"],["dc.contributor.author","Zanello, Marc"],["dc.contributor.author","Waha, Andreas"],["dc.contributor.author","Varlet, Pascale"],["dc.contributor.author","Pietsch, Torsten"],["dc.date.accessioned","2019-07-09T11:51:43Z"],["dc.date.available","2019-07-09T11:51:43Z"],["dc.date.issued","2019"],["dc.description.abstract","The recently described malignant neuro-epithelial tumors with histone H3F3A point mutations at G34 (NET-H3-G34) occur most often in cerebral hemispheres of teenagers and young adults, and have a generally adverse prognosis. These tumors have been histologically classified as glioblastoma or primitive neuroectodermal tumor (PNET) in the past, and have not been defined as a separate entity in the revised WHO classification of tumors of the CNS 2016. Here, we report two cases of NET-H3-G34 with glial and dysplastic ganglion cell components affecting teenagers. Patients were treated with surgery and radiochemotherapy with temozolomide. One patient underwent partial resection and deceased 21 months after diagnosis, while the other patient is alive without evidence of disease 15 months after total resection. So far, a dysplastic ganglion cell component has not been described in NET-H-G34, and its presence raises a possible relation to (anaplastic) gangliogliomas. Genome-wide copy number analysis did not provide unequivocal evidence that these tumors represent anaplastic variants of gangliogliomas, as opposed to NET-H3-G34. Our observations expand the morphologic spectrum of NET-H3-G34. Further cases of NET-H3-G34 with dysplastic ganglion cells should be clinically followed to find differences or similarities in their biological behavior, as compared to NET-H3-G34 and anaplastic gangliogliomas."],["dc.identifier.doi","10.1186/s40478-019-0731-5"],["dc.identifier.pmid","31109382"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16172"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59991"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","H3F3A-G34R mutant high grade neuroepithelial neoplasms with glial and dysplastic ganglion cell components"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]