ArticleNeuro-oncology2015
Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis.
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
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18citing papers in PubMed, 3 pooled it
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Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Prognostic Significance of Immunohistochemical Markers and Genetic Alterations in Malignant Peripheral Nerve Sheath Tumors: A Systematic Review.Frontiers in oncology · 2020Pooled it
- Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.PloS one · 2017Pooled it
- Current status and recommendations for biomarkers and biobanking in neurofibromatosis.Neurology · 2016Guideline
- Metabolic and behavioral effects of neurofibromin result from differential recruitment of MAPK and mTOR signaling.PLoS genetics · 2026Article
- Review
- Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2.Epigenomes · 2025Review
- Unraveling novel variants in the NF1 gene and investigating potential therapeutic strategies.Scientific reports · 2025Article
- A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.Cancers · 2025Review
- Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use.Neurology · 2021Article
- Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line.Scientific reports · 2021Article
- Promoter Methylation Status and Expression Levels of RASSF1A Gene in Different Phases of Acute Lymphoblastic Leukemia (ALL).International journal of hematology-oncology and stem cell research · 2021Article
- Genetics of human malignant peripheral nerve sheath tumors.Neuro-oncology advances · 2020Review
- Article
- Drug sensitivity and resistance testing identifies PLK1 inhibitors and gemcitabine as potent drugs for malignant peripheral nerve sheath tumors.Molecular oncology · 2017Article
- The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.The American journal of pathology · 2016Review
- Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Clinical utility of RASSF1A methylation in human malignancies.British journal of cancer · 2015Review
- Neurofibromatosis-related tumors: emerging biology and therapies.Current opinion in pediatrics · 2015Review
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Authors and funding
11 authors at 4 institutions in 4 countries.
Stine A DanielsenDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Guro E LindDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Matthias KolbergDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Maren HølandDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Bodil BjerkehagenDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Kirsten Sundby HallDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Eva van den BergDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Fredrik MertensDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Sigbjørn SmelandDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Piero PicciDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Ragnhild A LotheDepartment of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (S.A.D., G.E.L., M.K., M.H., R.A.L.); Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (M.H., S.S.); Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway (S.A.D., G.E.L., R.A.L.); Department of Pathology (B.B), Division of Diagnostics and Intervention and Department of Oncology, Division of Cancer, Surgery and Transplantation, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway (K.S.H., S.S.); Department of Medical Genetics, University Hospital of Groningen, The Netherlands (E.v.d.B.); Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden (F.M.); Laboratory of Oncologic Research of the Istituto Ortopedico Rizzoli, Bologna, Italy (P.P.).
Istituto Ortopedico Rizzoli · ITNorwegian Cancer Society · NOSkåne University Hospital · SEUniversity Medical Center Groningen · NL
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalignant peripheral nerve sheath tumor (MPNST) is a rare and highly aggressive disease with no evidence of effect from adjuvant therapy. It is further associated with the hereditary syndrome neurofibromatosis type 1 (NF1). Silencing of the tumor suppressor gene RASSF1A through DNA promoter hypermethylation is known to be involved in cancer development, but its impact in MPNSTs remains unsettled.
methodsThe RASSF1A promoter was analyzed by methylation-specific PCR in 113 specimens, including 44 NF1-associated MPNSTs, 47 sporadic MPNSTs, 21 benign neurofibromas, and 1 nonneoplastic nerve sheath control.
resultsRASSF1A methylation was found only in the malignant samples (60%) and identified a subgroup among patients with NF1-associated MPNST with a poor prognosis. These patients had a mean 5-year disease-specific survival of 27.3 months (95% CI: 17.2-37.4) versus 47.4 months (95% CI: 37.5-57.2) for NF1 patients with unmethylated promoters, P = 0.014. In multivariate Cox regression analysis, methylated RASSF1A remained an adverse prognostic factor independent of clinical risk factors, P = .013 (hazard ratio: 5.2; 95% CI: 1.4-19.4).
conclusionA considerable number of MPNST samples display hypermethylation of the RASSF1A gene promoter, and for these tumors, this is the first molecular marker that if validated can characterize a subgroup of patients with inferior prognosis, restricted to individuals with NF1.
Indexed as
DNA MethylationAdolescentAdultAgedChildFemaleHumansKaplan-Meier EstimateMaleMiddle AgedNeurilemmomaNeurofibromatosis 1PrognosisPromoter Regions, GeneticTumor Suppressor ProteinsYoung AdultRASSF1 protein, humanTumor Suppressor ProteinsmethylationMPNSTNF1RASSF1Asurvival
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