ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06114004 (Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas), which is not on this map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas
Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
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- Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2.Epigenomes · 2025Review
- 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
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- Conditionally replicative adenovirus as a therapy for malignant peripheral nerve sheath tumors.Molecular therapy. Oncology · 2024Article
- Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2024Review
- High Expression of ZNF208 Predicts Better Prognosis and Suppresses the Tumorigenesis of Breast Cancer.Clinical Medicine Insights. Oncology · 2024Article
- FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.International journal of molecular sciences · 2023Review
- MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Genetic Variation in theFrontiers in genetics · 2022Article
- The Role of ER Stress-Related Phenomena in the Biology of Malignant Peripheral Nerve Sheath Tumors.International journal of molecular sciences · 2021Review
- Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use.Neurology · 2021Article
- Chromosomal translocations inactivating CDKN2A support a single path for malignant peripheral nerve sheath tumor initiation.Human genetics · 2021Article
- Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study.PLoS medicine · 2021Article
- Chromosome 8 gain is associated with high-grade transformation in MPNST.JCI insight · 2021Article
- Whole exome sequencing reveals the maintained polyclonal nature from primary to metastatic malignant peripheral nerve sheath tumor in two patients with NF1.Neuro-oncology advances · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeMalignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma. EXPERIMENTAL
designWhole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis.
resultsThere was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo.
conclusionsCollectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study.
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