Neurofibroma Development in Neurofibromatosis Type 1: Insights from Cellular Origin and Schwann Cell Lineage Development

Background: Neurofibromatosis type 1 (NF1), a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns, is caused by mutations in the NF1 gene and subsequent inactivation of its encoded neurofibromin. Neurofibromin is a tumor suppressor protein involved in the downregulation of Ra...

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Bibliographic Details
Published in:Cancers 2022-09, Vol.14 (18), p.4513
Main Authors: Ge, Ling-Ling, Xing, Ming-Yan, Zhang, Hai-Bing, Wang, Zhi-Chao
Format: Article
Language:English
Subjects:
Cell lineage
Complications and side effects
Development and progression
Developmental stages
Fibroblasts
Genes
Genetic disorders
Genetic transformation
Health aspects
Hypotheses
Malignancy
Mutation
Neonates
Neurofibroma
Neurofibromatosis
Neurofibromin 1
Neurological disorders
Pathogenesis
Peripheral nerves
Proteins
Puberty
Recklinghausen's disease
Review
Reviews
Risk factors
Schwann cells
Tumor suppressor genes
Tumors
Citations: Items that this one cites
Items that cite this one
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Summary:Background: Neurofibromatosis type 1 (NF1), a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns, is caused by mutations in the NF1 gene and subsequent inactivation of its encoded neurofibromin. Neurofibromin is a tumor suppressor protein involved in the downregulation of Ras signaling. Despite a diverse clinical spectrum, one of several hallmarks of NF1 is a peripheral nerve sheath tumor (PNST), which comprises mixed nervous and fibrous components. The distinct spatiotemporal characteristics of plexiform and cutaneous neurofibromas have prompted hypotheses about the origin and developmental features of these tumors, involving various cellular transition processes. Methods: We retrieved published literature from PubMed, EMBASE, and Web of Science up to 21 June 2022 and searched references cited in the selected studies to identify other relevant papers. Original articles reporting the pathogenesis of PNSTs during development were included in this review. We highlighted the Schwann cell (SC) lineage shift to better present the evolution of its corresponding cellular origin hypothesis and its important effects on the progression and malignant transformation of neurofibromas. Conclusions: In this review, we summarized the vast array of evidence obtained on the full range of neurofibroma development based on cellular and molecular pathogenesis. By integrating findings relating to tumor formation, growth, and malignancy, we hope to reveal the role of SC lineage shift as well as the combined impact of additional determinants in the natural history of PNSTs.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14184513