:: Volume 29, Issue 2 (Summer 2019) ::
MEDICAL SCIENCES 2019, 29(2): 101-116 Back to browse issues page
The molecular genetics of neurofibromatosis type 1 and its future prospective
Mohammad Reza Nooridaloii 1, Elham Boustanipour2
1- , Department of Medical Genetics, Faculty of Medicine Tehran of Medical Sciences, Tehran, Iran , nooridaloii@sina.tums.ac.ir
2- MSc Student, Department of Medical Genetics, Faculty of Medicine Tehran of Medical Sciences, Tehran, Iran
Abstract:   (4020 Views)
Abstract
 
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that is caused through loss of function mutations of a tumor suppressor gene termed neurofibromin 1. Therapeutic decisions are presently restricted for NF1-associated tumors, where treatment is often restricted to thorough surgical resection with perfect margins. In this review article, the multifunctional role of neurofibromin in tumor suppression has been discussed. While neurofibromin inhibits proliferative growth through blockade RAS-mediated signal transduction, neurofibromin should also be considered as a modulator of cell motility and cell adhesion. Through interfacing with the cytoskeleton and membrane structures, neurofibromin acts as a negative regulator of RHO/ROCK signaling pathways involved in cytoskeletal dynamics that are involved in proper neuronal expansion.
The loss of function of neurofibromin through genetic mutation results in heightened cell proliferation and migration, predisposing NF1 patients to cancer. Malignant peripheral nerve sheath tumors (MPNSTs) can be developed from benign neurofibromas and are the main cause of death amongst NF1 patients. Recent researchers in MPNSTs have been attempting to reveal key molecular events that lead MPNSTs to malignancy. Advances regarding malignant drivers involved in cell migration, cell invasion and angiogenic signaling are discussed in this review, where these findings will likely influence future therapies for both NF1 and related sporadic cancers.
Keywords: Neurofibromatosis type 1, Plexiform Neurofibromatosis, MPNST.
 
Keywords: Neurofibromatosis type 1, Plexiform Neurofibromatosis, MPNST.
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Semi-pilot: Review | Subject: Genetic
Received: 2018/11/26 | Accepted: 2019/01/13 | Published: 2019/06/16
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