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| 001 | 302878 | ||
| 005 | 20250718114120.0 | ||
| 024 | 7 | _ | |a 10.1186/s13059-025-03670-y |2 doi |
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| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Costa, Ana Luisa |b 0 |
| 245 | _ | _ | |a A new IDH-independent hypermethylation phenotype is associated with astrocyte-like cell state in glioblastoma. |
| 260 | _ | _ | |a London |c 2025 |b BioMed Central |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1752751081_14020 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a Isocitrate Dehydrogenase |0 EC 1.1.1.41 |2 NLM Chemicals |
| 650 | _ | 2 | |a Glioblastoma: genetics |2 MeSH |
| 650 | _ | 2 | |a Glioblastoma: pathology |2 MeSH |
| 650 | _ | 2 | |a Glioblastoma: metabolism |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a DNA Methylation |2 MeSH |
| 650 | _ | 2 | |a Isocitrate Dehydrogenase: genetics |2 MeSH |
| 650 | _ | 2 | |a Isocitrate Dehydrogenase: metabolism |2 MeSH |
| 650 | _ | 2 | |a Astrocytes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Astrocytes: pathology |2 MeSH |
| 650 | _ | 2 | |a Phenotype |2 MeSH |
| 650 | _ | 2 | |a Cell Line, Tumor |2 MeSH |
| 650 | _ | 2 | |a CpG Islands |2 MeSH |
| 650 | _ | 2 | |a Epigenesis, Genetic |2 MeSH |
| 650 | _ | 2 | |a Gene Expression Regulation, Neoplastic |2 MeSH |
| 650 | _ | 2 | |a Brain Neoplasms: genetics |2 MeSH |
| 650 | _ | 2 | |a Brain Neoplasms: pathology |2 MeSH |
| 700 | 1 | _ | |a Doncevic, Daria |b 1 |
| 700 | 1 | _ | |a Wu, Yonghe |0 P:(DE-He78)048cd293ec9a8bd9be8a97dde02ee343 |b 2 |
| 700 | 1 | _ | |a Yang, Lin |b 3 |
| 700 | 1 | _ | |a Man, Ka Hou |0 P:(DE-He78)54ffbd220f4f40801144e564197dd3d4 |b 4 |
| 700 | 1 | _ | |a Spreng, Anna-Sophie |0 P:(DE-He78)c4c258d44a86b1ab0d1c5d7370a4a916 |b 5 |u dkfz |
| 700 | 1 | _ | |a Winter, Hannah |b 6 |
| 700 | 1 | _ | |a Fletcher, Michael |0 P:(DE-He78)531cf6e04ba45b3c088cd4d4d3cc3c36 |b 7 |
| 700 | 1 | _ | |a Radlwimmer, Bernhard |0 P:(DE-He78)d1939d434dd885fad08106329e3db719 |b 8 |u dkfz |
| 700 | 1 | _ | |a Herrmann, Carl |b 9 |
| 773 | _ | _ | |a 10.1186/s13059-025-03670-y |g Vol. 26, no. 1, p. 192 |0 PERI:(DE-600)2040529-7 |n 1 |p 192 |t Genome biology |v 26 |y 2025 |x 1465-6906 |
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