Neurofibromatosis and Glioblastoma Variation Dynamics

Neurofibromatosis type 1 (NF1) is a hereditary tumour predisposition syndrome arising from loss-of-function mutations in the NF1 tumour suppressor gene, leading to aberrant RAS–MAPK signalling. While benign neurofibromas are hallmark lesions, patients harbour an elevated risk of high-grade gliomas, including glioblastoma. Glioblastoma exhibits pronounced intra- and inter-tumoral heterogeneity, driven by genetic alterations (NF1 inactivation, TP53, PTEN), epigenetic reprogramming and dynamic interactions with the microenvironment. Variation dynamics encompass clonal evolution under hypoxia, therapy-induced selection pressures and differential cytokine/chemokine secretion that fosters a mesenchymal phenotype. Understanding these processes is crucial for stratifying patients, guiding targeted interventions and improving prognostic assessment. Recent advances elucidate how NF1 status modulates tumour cell behaviour, epigenetic landscapes and secreted mediators, highlighting novel vulnerabilities in both IDH-wildtype and variant glioblastoma subtypes across paediatric and adult populations.

Research from Nature Portfolio

High-throughput screening of epigenetic and cell-cycle targets in glioblastoma cell lines under both normoxic and hypoxic conditions has identified the PRMT5 inhibitor onametostat as a potent suppressor of proliferation and viability. Onametostat induces cell-cycle arrest, disrupts RNA splicing and down-regulates key survival pathways across MGMT-positive and MGMT-negative models, suggesting broad applicability even in chemo- and radio-resistant contexts. In parallel, mechanistic studies using siRNA-mediated NF1 knockdown in glioma lines have revealed upregulated secretion of platelet-derived growth factor AA, chitinase-3-like protein 1, interleukin-8 and endoglin. These factors are implicated in mesenchymal identity and remodelling of the tumour microenvironment, linking NF1 loss directly to cytokine-driven heterogeneity.

Neurofibromatosis and Glioblastoma Variation Dynamics publication trend

The graph below shows the total number of articles in neurofibromatosis and glioblastoma variation dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Neurofibromatosis type 1 (NF1): A genetic disorder caused by mutations in the NF1 gene, leading to dysregulated RAS signalling and predisposition to tumours.

Glioblastoma: The most aggressive form of primary brain tumour characterised by rapid growth, heterogeneity and poor prognosis.

IDH-wildtype: Glioblastoma lacking mutations in isocitrate dehydrogenase genes, typically associated with a more aggressive clinical course.

PRMT5 inhibitor (onametostat): A compound targeting protein arginine methyltransferase 5 to disrupt epigenetic regulation and cell-cycle progression in tumour cells.

Immunohistochemistry (IHC): A laboratory technique that uses antibodies to detect specific proteins in tissue sections, informing on expression and localisation.

References

1. NF1 expression profiling in IDH-wildtype glioblastoma: genomic associations and survival outcomes. Acta Neuropathologica Communications (2024).
2. Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions. Scientific Reports (2024).
3. Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro. Scientific Reports (2018).
4. Glioblastoma in a female neurofibromatosis 1 patient without IDH1, BRAF V600E, and TERT promoter mutations. Medicine (2021).