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000302878 1001_ $$aCosta, Ana Luisa$$b0
000302878 245__ $$aA new IDH-independent hypermethylation phenotype is associated with astrocyte-like cell state in glioblastoma.
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000302878 520__ $$aDNA 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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000302878 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aIsocitrate Dehydrogenase
000302878 650_2 $$2MeSH$$aGlioblastoma: genetics
000302878 650_2 $$2MeSH$$aGlioblastoma: pathology
000302878 650_2 $$2MeSH$$aGlioblastoma: metabolism
000302878 650_2 $$2MeSH$$aHumans
000302878 650_2 $$2MeSH$$aDNA Methylation
000302878 650_2 $$2MeSH$$aIsocitrate Dehydrogenase: genetics
000302878 650_2 $$2MeSH$$aIsocitrate Dehydrogenase: metabolism
000302878 650_2 $$2MeSH$$aAstrocytes: metabolism
000302878 650_2 $$2MeSH$$aAstrocytes: pathology
000302878 650_2 $$2MeSH$$aPhenotype
000302878 650_2 $$2MeSH$$aCell Line, Tumor
000302878 650_2 $$2MeSH$$aCpG Islands
000302878 650_2 $$2MeSH$$aEpigenesis, Genetic
000302878 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000302878 650_2 $$2MeSH$$aBrain Neoplasms: genetics
000302878 650_2 $$2MeSH$$aBrain Neoplasms: pathology
000302878 7001_ $$aDoncevic, Daria$$b1
000302878 7001_ $$0P:(DE-He78)048cd293ec9a8bd9be8a97dde02ee343$$aWu, Yonghe$$b2
000302878 7001_ $$aYang, Lin$$b3
000302878 7001_ $$0P:(DE-He78)54ffbd220f4f40801144e564197dd3d4$$aMan, Ka Hou$$b4
000302878 7001_ $$0P:(DE-He78)c4c258d44a86b1ab0d1c5d7370a4a916$$aSpreng, Anna-Sophie$$b5$$udkfz
000302878 7001_ $$aWinter, Hannah$$b6
000302878 7001_ $$0P:(DE-He78)531cf6e04ba45b3c088cd4d4d3cc3c36$$aFletcher, Michael$$b7
000302878 7001_ $$0P:(DE-He78)d1939d434dd885fad08106329e3db719$$aRadlwimmer, Bernhard$$b8$$udkfz
000302878 7001_ $$aHerrmann, Carl$$b9
000302878 773__ $$0PERI:(DE-600)2040529-7$$a10.1186/s13059-025-03670-y$$gVol. 26, no. 1, p. 192$$n1$$p192$$tGenome biology$$v26$$x1465-6906$$y2025
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