{"id":"VC0141","type":"paper","title":"Acquired genetic and cell-state changes in IDH-mutant glioma progression","authors_or_org":"Johnson KC, Spitzer A, Varn FS, Nomura M, Garofano L, Chowdhury T, Lipsa A, Zhang L, ... Suvà ML, Iavarone A, Tirosh I, Verhaak RGW (51 authors; first five contributed equally)","date":"2026-06-03","year":"2026","venue":"Nature","url":"https://www.nature.com/articles/s41586-026-10612-6","doi":"10.1038/s41586-026-10612-6","pmid":"","brain_tumor_focus":"yes","tags":["glioma","IDH-mutant","astrocytoma","oligodendroglioma","snRNA-seq","scATAC","cell states","mesenchymal-like","recurrence","longitudinal","multi-omics"],"tag_slugs":["glioma","idh","multi-omics"],"tag_labels":["Glioma","IDH","Multi-omics"],"tag_labels_zh":["胶质瘤","IDH 突变","多组学"],"unmapped_tags":["astrocytoma","oligodendroglioma","snRNA-seq","scATAC","cell states","mesenchymal-like","recurrence","longitudinal"],"one_line_summary_en":"Open access. Integrates snRNA-seq, chromatin accessibility and bulk DNA/RNA sequencing of 75 temporally separated IDH-mutant gliomas from 35 patients (oligodendroglioma and astrocytoma). Malignant cell states resemble stages of normal glial–neuronal lineage development or a reactive mesenchymal-like state, mirroring states described in IDH-wildtype glioblastoma, with chromatin profiles comparable between both tumour types. Two longitudinal state-transition patterns: reduced lineage differentiation and more proliferative cells at recurrence, enriched in gliomas that acquired recurrence-associated genetic events (treatment-associated hypermutation, copy-number changes, cell-cycle alterations); and increased mesenchymal-like abundance independent of acquired genetic alterations, coinciding with elevated macrophage expression. IDH-mutant, not IDH-wildtype GBM. The abstract does not use the term 'convergence'. Data: GEO (GSE326221, GSE327580 and others), Synapse (care_idh_mutant), EGA EGAS50000001727, DUOS-000475; code: github.com/Kcjohnson/care-glass and care_idh_mut.","one_line_summary_zh":"开放获取。整合 75 例时间上分离的 IDH 突变型胶质瘤（来自 35 例患者，含少突胶质细胞瘤与星形细胞瘤）的单核转录组、染色质可及性及整体 DNA/RNA 测序。恶性细胞状态类似正常胶质-神经谱系发育阶段或反应性间充质样状态，与 IDH 野生型胶质母细胞瘤中描述的状态相呼应，且两种肿瘤类型的染色质可及性谱相当。纵向分析提示两种状态转变模式：复发时谱系分化降低、增殖性细胞增多，见于获得复发相关遗传事件（治疗相关超突变、拷贝数改变、细胞周期改变）的肿瘤；间充质样状态丰度增加则与获得性遗传改变无关，而与巨噬细胞表达升高同时出现。研究对象为 IDH 突变型而非 IDH 野生型 GBM。摘要中未使用“趋同”一词。数据：GEO（GSE326221、GSE327580 等）、Synapse（care_idh_mutant）、EGA EGAS50000001727、DUOS-000475；代码：github.com/Kcjohnson/care-glass 与 care_idh_mut。","verified":"yes","verification_source":"Nature article page via doi.org redirect (publisher; fetched 2026-10-15: title, authors, dates [received 2024-10-05, accepted 2026-04-30, published online 2026-06-03; Nature 655:1048–1059, issue 23 Jul 2026], abstract, data/code availability); PMID not looked up","page_url":"https://gliostate.com/library/VC0141/","api_url":"https://gliostate.com/api/items/VC0141.json","sameAs":["https://doi.org/10.1038/s41586-026-10612-6","https://www.nature.com/articles/s41586-026-10612-6"],"is_preprint":false,"facets":{"type":"https://gliostate.com/library/type/paper/","year":"https://gliostate.com/library/year/2026/","tags":["https://gliostate.com/library/tag/glioma/","https://gliostate.com/library/tag/idh/","https://gliostate.com/library/tag/multi-omics/"]},"cited_by":[{"id":"transition-therapy-induced-plasticity","type":"transition","title_en":"Therapy-induced plasticity in glioblastoma","title_zh":"胶质母细胞瘤的治疗诱导可塑性","url":"https://gliostate.com/transitions/therapy-induced-plasticity/","api_url":"https://gliostate.com/api/topics/transition-therapy-induced-plasticity.json"}],"related":[{"id":"VC0140","title":"Divergent genomic evolution in astrocytomas and oligodendrogliomas","shared_tags":["glioma","idh"],"page_url":"https://gliostate.com/library/VC0140/","api_url":"https://gliostate.com/api/items/VC0140.json"},{"id":"VC0139","title":"Engineered regulatory states resolve context-dependent genetics in macular degeneration","shared_tags":["multi-omics"],"page_url":"https://gliostate.com/library/VC0139/","api_url":"https://gliostate.com/api/items/VC0139.json"},{"id":"VC0062","title":"Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma.","shared_tags":["multi-omics"],"page_url":"https://gliostate.com/library/VC0062/","api_url":"https://gliostate.com/api/items/VC0062.json"},{"id":"VC0090","title":"A State-Resolved Single-Cell and Spatial Atlas Reveals IDH-Associated Differences in Malignant and Immune Architecture in Diffuse Glioma.","shared_tags":["idh"],"page_url":"https://gliostate.com/library/VC0090/","api_url":"https://gliostate.com/api/items/VC0090.json"},{"id":"VC0063","title":"Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.","shared_tags":["idh"],"page_url":"https://gliostate.com/library/VC0063/","api_url":"https://gliostate.com/api/items/VC0063.json"},{"id":"VC0134","title":"TumorTwin: a Python framework for patient-specific digital twins in oncology","shared_tags":["glioma"],"page_url":"https://gliostate.com/library/VC0134/","api_url":"https://gliostate.com/api/items/VC0134.json"}]}