Aberrant Gene Expression in NF1-Mediated Oncogenesis. Addendum

摘要

Neurofibromatosis type I (NF1) is a familial multisystem disease that occurs in approximately one in 3,500 people designating it as one of the most common autosomal-dominant human diseases. Approximately 5% of all NF1 patients develop malignant tumors making it the most common tumor-predisposing disease in humans. Mutations in the NF1 gene, which functions as a tumor suppressor, are considered to be the primary cause for the disease. NF1 is a very large protein composed of 2818 amino acids. A small segment of the protein has been demonstrated to function as a negative regulator of the Ras family of small GTPases. However the biochemical functions of the remaining protein remains currently unknown. Thus, it seems likely that NF1 mediates its tumor suppressor activities through Ras-dependent as well as Ras-independent mechanisms. Therefore, we propose to determine what changes in gene expression occur as a result of loss of NF1 expression and to determine which expression changes are a consequence of Ras activity and which are not. We believe this information will lead to a more complete understanding of how NF1 mediates tumorigenesis and identify novel targets for the rational design of anti-cancer therapeutics against neurofibromatosis.