Abstract
Neurofibromatosis type 1 (NF1; MIM# 162200) is an autosomal dominant neurocutaneous disease that is aggravated by an enhanced incidence of malignant tumors deriving from the neural crest (Riccardi 1992). The birth incidence of NF1 is ≈1/3000 to 1/3500. Patients with NF1 display multiple café-au-lait macules (CALMs) at birth or during early childhood, and develop neurofibromas as adults. NF1-associated malignant tumors from neural crest origin comprise malignant schwannoma (neurofibrosarcoma), medulloblastoma, astrocytoma, and pheochromocytoma.
The disease is caused by germline mutations that inactivate one neurofibromin gene on the long arm of chromosome 17 (17q11.2). The protein neurofibromin encoded by the NF1 gene is a RAS-specific GTPase-activating protein that functions as a negative regulator of the RAS pathway (Xu et al. 1990). It can be considered a tumor suppressor gene as inactivation of both copies of the NF1 gene can be found in NF1-associated malignant schwannoma and pheochromocytoma (Legius et al. 1993; Xu et al. 1992). Inactivation of both NF1 alleles as well as loss of heterozygo-sity (LOH) of microsatellite DNA within the NF1 gene could also be demonstrated in benign NF1-associated neurofibromas (Rutkowski et al. 2000; Sawada et al. 1996; Serra et al. 1997).
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Rübben, A. (2010). Neurofibromatosis Type 1-Associated Malignant Melanoma: Molecular Evidence of Inactivation of the NF1 Gene. In: Hayat, M. (eds) Methods of Cancer Diagnosis, Therapy, and Prognosis. Methods of Cancer Diagnosis, Therapy and Prognosis, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2918-8_25
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