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@ARTICLE{Costa:302878,
      author       = {A. L. Costa and D. Doncevic and Y. Wu$^*$ and L. Yang and
                      K. H. Man$^*$ and A.-S. Spreng$^*$ and H. Winter and M.
                      Fletcher$^*$ and B. Radlwimmer$^*$ and C. Herrmann},
      title        = {{A} new {IDH}-independent hypermethylation phenotype is
                      associated with astrocyte-like cell state in glioblastoma.},
      journal      = {Genome biology},
      volume       = {26},
      number       = {1},
      issn         = {1465-6906},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-01418},
      pages        = {192},
      year         = {2025},
      abstract     = {DNA methylation plays a crucial role in cancer development
                      and progression and has been linked to genetically and
                      clinically distinct tumor classes, including IDH-mutated and
                      IDH-wildtype adult-type diffuse gliomas. Here, we identify a
                      CpG-island methylator phenotype (CIMP) that characterizes
                      the receptor tyrosine kinase 2 (RTK2) subtype of
                      IDH-wildtype glioblastoma.This RTK2-CIMP affects genomic
                      locations and cell functions distinct from those of IDH
                      mutation-associated IDH-CIMP and suppresses the expression
                      of its target genes. The RTK2-CIMP-region chromatin is
                      characterized by a combination of repressive and activating
                      marks, including polycomb-associated H3K27me3 and
                      enhancer-associated H3K4me1, consistent with DNA
                      methylation-mediated silencing of genes with bivalent-state
                      promoters in neural progenitor cells. Functionally,
                      RTK2-CIMP affects neuronal lineage genes and is
                      significantly associated with astrocyte-like glioblastoma,
                      suggesting that RTK2-CIMP is an epigenetic signature of the
                      astrocyte-like cell state. Furthermore, we demonstrate that
                      RTK2-CIMP can be induced by genetic manipulation in
                      glioblastoma cells.Our results suggest that RTK2-CIMP is a
                      key contributor to cell-state plasticity in glioblastoma.},
      keywords     = {Glioblastoma: genetics / Glioblastoma: pathology /
                      Glioblastoma: metabolism / Humans / DNA Methylation /
                      Isocitrate Dehydrogenase: genetics / Isocitrate
                      Dehydrogenase: metabolism / Astrocytes: metabolism /
                      Astrocytes: pathology / Phenotype / Cell Line, Tumor / CpG
                      Islands / Epigenesis, Genetic / Gene Expression Regulation,
                      Neoplastic / Brain Neoplasms: genetics / Brain Neoplasms:
                      pathology / Isocitrate Dehydrogenase (NLM Chemicals)},
      cin          = {B060},
      ddc          = {570},
      cid          = {I:(DE-He78)B060-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40611337},
      pmc          = {pmc:PMC12225510},
      doi          = {10.1186/s13059-025-03670-y},
      url          = {https://inrepo02.dkfz.de/record/302878},
}