[Pathogenic alterations within the neurofibromin gene in various cancers]

The product of the neurofibromin gene (NF1) belongs to the family of tumor suppressor proteins. Neurofibromin plays important roles in the negative regulation of signaling pathways where the Ras oncogen is involved. The protein and gene names were derived from the disease, neurofibromatosis type 1 that is caused by germline mutations in NF1 and inherited by an autosomal dominant manner. Besides germline mutations, acquired, somatic mutations are also observed in NF1 in several malignant and benign tumors. NF1 mutations have been identified in a great number of solid tumors, leukemias and malignant skin lesions (e.g. melanoma). Such mutations define certain subsets of gliomas. More specifically, a molecular subset of glioblastomas, termed the mesenchymal subtype, is most frequently associated with somatic NF1 deletions and mutations. The aim of this survey is to provide an overview of the most frequent alterations in the NF1 gene with their effects on the function of the protein and the biology of the cell, as well as of the resultant diseases. Simultaneously, we give some insight into ongoing research studies investigating abnormalities of NF1.