This section discusses the tumorigenesis of<unk>  in terms of genetics, cell signaling, histology and the cell cycle.<unk> n 1 gene This picture illustrates the structure of the<unk> 1 gene product,<unk> n 1. This protein is 2818 amino acids long with 3 alternatively spiced exons, 9a, 23a, and 48a. The IRA domains are hypothesized to function as negative regulators of RAS, along with the GRD domain in between them. The<unk> 1 gene is composed of 60 exons spanning 350kb of genomic data, and maps to chromosomal region 17qll.2. This gene codes for<unk> n which is a large 220-250 KDa cytoplasmic protein that is composed of 2,818 amino acids with three alternatively spliced exons (9a, 23a and 48a) in the encoding gene. The functional part of<unk> n is a GAP, or GTPase-activating protein. GAP accelerates the conversion of the active GTP-bound RAS to its inactive GDP-bound form, inactivating RAS and reducing RAS-mediated growth signaling. Loss of RAS control leads to increased activity of other signaling pathways including RAF, ERK1/2, PI3K, PAK and mTOR-S6 kinase. This increased activity of downstream RAS pathways might work together to increase cell growth and survival. Genes that code for proteins that regulate cell growth, such as<unk> 1 and TP53, are referred to as tumor suppressor genes.<unk> n has other growth-regulatory properties besides its ability to regulate RAS activity, but these other functions are poorly understood at this time. Schwann cells There are two kinds of Schwann cells, myelinating and nonmyelinating. While myelinating Schwann cells cover large diameter (>1 micrometer) peripheral nervous system (PNS) axons with myelin, nonmyelinating Schwann cells encapsulate small diameter PNS axons with their cytoplasmic processes. Nonmyelinating Schwann cells are the neoplastic element in<unk> s. This conglomeration of nonmyelinating Schwann cells and axons is called a Remak bundle. While nonmyelinating Schwann cells are the origin of<unk> s, the mutations that make them susceptible to this transformation occur in Schwann cell precursors during early nerve development. Mutated nonmyelinating Schwann cells do not form normal Remak bundles. Instead, they fail to properly surround and segregate target axons. It is unknown at this time why, if both types of Schwann cells exhibit bilallelic inactivation of the<unk> 1 gene, only the nonmyelinating variety give rise to<unk> s. Loss of tumor suppressor function<unk> s arise from nonmyelinating Schwann cells that only express the inactive version of the<unk> 1 gene, which leads to a complete loss of expression of functional<unk> n. While one defective allele may be inherited, loss of heterozygosity (LOH) must occur before a<unk>  can form; this is called the ‘two-hit hypothesis’. This LOH happens by the same mechanisms, such as oxidative DNA damage, that causes mutations in other cells. Once a nonmyelinating Schwann cell has suffered inactivation of its<unk> 1 genes, it begins to proliferate rapidly. This condition is called hyperplasia, which is cell growth beyond what is normally seen. However, despite increased numbers of nonmyelinating Schwann cells, there is no<unk>  yet. In order for the<unk>  to develop, cells that are heterozygous for the<unk> 1 gene must be recruited to the site. It has been hypothesized that the proliferating nonmyelinating Schwann cells secrete chemoattractants such as the KIT ligand, and angiogenic factors such as the heparin-binding growth factor midkine. These chemicals promote the migration of different kinds of cells that are heterozygous for the<unk> 1 gene into the hyperplastic lesions created by the nonmyelinating Schwann cells. These cell types include fibroblasts, perineurial cells, endothelial cells, and mast cells. The mast cells then secrete mitogens or survival factors that alter the developing tumor microenvironment and result in<unk>  formation. Dermal and plexiform<unk> s differ in later development stages, but the details are unclear at this point.
Neurofibroma
Palisaded encapsulated neuroma
Neuroma
Hemangioblastoma
Ameloblastoma
Ganglioneuroma
Ganglion cyst
Brenner tumour