Genes· 2026Q2
Architects of Aggression: The Molecular Blueprint of Glioma Progression
- 0citations
- Q2SCImago
- 2026year
Short summary
Glioblastoma (GBM) progression is driven by non-genetic plasticity, including transcriptomic continua, functional integration with host brain via synapses, and an immunologically cold niche, enabling rapid adaptive remodeling under therapy.
AI-generated from the title and abstract; the full text is not read.
Key points
- Glioblastoma (GBM) progression is significantly driven by non-genetic plasticity rather than solely genetic mutations.
- Single-nucleus sequencing reveals a fluid transcriptomic continuum and hybrid cell states within GBM tumors.
- GBM cells integrate functionally with the host brain via electrochemical synapses.
- The tumor microenvironment is an immunologically cold niche dominated by SPP1+ myeloid cells.
- Therapy induces rapid adaptive remodeling, selecting for hypermutator and SASP phenotypes, leading to aggressive recurrence.
AI-generated from the title and abstract; the full text is not read.
Abstract
Despite decades of clinical validation, glioblastoma (GBM) treatment remains tethered to a dismal 15-to-16-month survival plateau, heavily thwarted by the ys blood–brain barrier (BBB) and profound cellular heterogeneity. While the 2021 World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) fundamentally reoriented diagnosis around definitive molecular signatures, such as isocitrate dehydrogenase (IDH)-wildtype status, epidermal growth factor receptor (EGFR) amplification, and +7/−10 chromosomal alterations, the ultimate obstacle to clinical efficacy is the tumor’s intense non-genetic plasticity. Malignant cells reject rigid hierarchies; single-nucleus insights reveal a fluid transcriptomic continuum spanning neurodevelopmental lineages, novel glia-like or neuronal-like states, and highly resilient proneural-mesenchymal (PM) hybrid populations. This intrinsic dynamism is reinforced by functional neuro-gliomal integration into the host brain via electrochemical TM synapses, an immunologically cold niche dominated by secreted phosphoprotein 1 (SPP1+) myeloid cells, and a self-reinforcing hypoxic-angiogenic loop. Under cytotoxic therapy, these networks execute rapid adaptive remodeling, selecting for hypermutator phenotypes and specialized senescence-associated secretory phenotypes (SASP) that dictate aggressive recurrence.
The authors' abstract, as published at the source. Genes, 2026 · DOI ↗
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Field: Genetics (Medicine)
GeneticsMedicine