Acquired genetic and cell-state changes in IDH-mutant glioma progression

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.

Authors / organisation

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)

Venue

Nature

Date

2026-06-03

Type

paper

Year

2026

DOI

10.1038/s41586-026-10612-6

Source

https://www.nature.com/articles/s41586-026-10612-6

Verification

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

GliomaIDHMulti-omicsastrocytomaoligodendrogliomasnRNA-seqscATACcell statesmesenchymal-likerecurrencelongitudinal

Open in the searchable library → · JSON