6 Neurofibromatosis Type I: From Genetic Mutation to Tumor Formation

摘要: Neurofibromatosis type I (NF1) is one of the most common genetic disorders nervous system. Inheritance occurs through a germline deletion or loss‐of‐function mutation neurofibromatosis 1 gene. The NF1 gene codes for protein neurofibromin, which contains GTPase‐ activating (GAP)‐related domain (NF1‐GRD) and functions as negative regulator small G proteins, including Ras. hyperactivation Ras that results from loss neurofibromin thought to contribute various types lesions are prevalent in NF1. Individuals with predisposed number pathologies peripheral nerve sheath tumors, hyperpigmentation skin, iris, skeletal lesions, vascular abnormalities, learning disorders, an increased incidence several malignancies. Malignant tumors (MPNST) features These constitute major cause morbidity mortality individuals since only current treatment these (surgical removal) not effective. This chapter discusses clinical characteristics NF1, mutations gene, animal models expression function therapeutic approaches disease. understanding etiology MPNST formation also summarized. List Abbreviations: ANGPT1, angiopoietin‐1; bFGF, basic fibroblast growth factor; cAMP, cyclic adenosine monophosphate; CNS, central system; DNA, deoxyribonucleic acid; EGF, epidermal EGFR, factor receptor; FGF2, 2; FGF7, 7; FGFR3, receptor 3; FTI, farnesyltransferase inhibitor; GAP, protein; GDP, guanosine diphosphate; GM‐CSF, granulocyte–macrophage colony‐stimulating GRD, GAP‐related domain; GGF2, glial GROa, growth‐related oncoprotein a; GTP, triphosphate; GTPase, triphosphatase; HGF, hepatocyte IGF‐1, insulin‐ like 1; LOH, heterozygosity; MAPK, mitogen‐activated kinase; MDK, midkine; MPNST, malignant tumor; mRNA, messenger ribonucleic I; gene; NF1‐GRD, NRP‐1, neuropilin PDGF, platelet‐derived PEDF, pigment epithelium‐derived PGE, prostaglandin; PI3K, phosphatidylinositol‐3‐kinase; PKA, kinase A; PlGF, placental Rb, retinoblastoma RNA, SCF, stem cell SPARC, secreted acidic rich cysteine; TGF‐b1, transforming b1; TGF‐bRII, TGFb TIMP‐1, tissue inhibitor metalloproteinase TIMP‐2, TSP‐1, thrombospondin‐1; uPA, urokinase plasminogen activator; uPAR, activator VEGF, endothelial VEGFC, C