ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors.Neuro-oncology advances · 2026Review
- IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors.Neuro-oncology advances · 2026Review
- FAP expression as a marker of malignant transformation enabling in vivo characterization in peripheral nerve sheath tumors: a multimodal and translational study.Acta neuropathologica · 2026Article
- Review
- Review
- Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.Neuro-oncology · 2025Article
- Spatial transcriptomics: Advances and challenges in peripheral nerve sheath tumor.Neuro-oncology · 2025Article
- Single-cell tumor microenvironment profiling informs a circulating proteome test for the interception of malignant transformation in NF1 nerve sheath tumors.Research square · 2025Article
- The RXR Agonist MSU-42011 Reduces Tumor Burden in a Murine Preclinical NF1-Deficient Model.Cancers · 2025Article
- DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis Type 1.Neuro-oncology · 2025Article
- A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.Cancers · 2025Review
- UBR5 in Tumor Biology: Exploring Mechanisms of Immune Regulation and Possible Therapeutic Implications in MPNST.Cancers · 2025Review
- Mannan-Decorated Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Antitumor Immune Response by Modulating the Tumor Microenvironment.Journal of functional biomaterials · 2024Review
- Past, Present, and Future Therapeutic Strategies for NF-1-Associated Tumors.Current oncology reports · 2024Review
- STING activation reprograms the microenvironment to sensitize NF1-related malignant peripheral nerve sheath tumors for immunotherapy.The Journal of clinical investigation · 2024Article
- TheCancers · 2024Review
- Malignant peripheral nerve sheath tumors in neurofibromatosis type 1 arise from distinct nodular lesions: A retrospective imaging analysis.Neuro-oncology advancesArticle
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
purposePlexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss. Although genomic studies have uncovered key driver events promoting tumor progression, the transcriptional changes preceding malignant transformation remain poorly defined. EXPERIMENTAL
designHere we resolve gene-expression profiles in PNST across the neurofibroma-to-MPNST continuum in NF1 patients and mouse models, revealing early molecular features associated with neurofibroma evolution and transformation.
resultsOur findings demonstrate that ANF exhibit enhanced signatures of antigen presentation and immune response, which are suppressed as malignant transformation ensues. MPNST further displayed deregulated survival and mitotic fidelity pathways, and targeting key mediators of these pathways, CENPF and BIRC5, disrupted the growth and viability of human MPNST cell lines and primary murine Nf1-Cdkn2a-mutant Schwann cell precursors. Finally, neurofibromas contiguous with MPNST manifested distinct alterations in core oncogenic and immune surveillance programs, suggesting that early molecular events driving disease progression may precede histopathologic evidence of malignancy.
conclusionsIf validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathologic diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.
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