title: Genetic and cellular defects contributing to benign tumor formation in neurofibromatosis type 1.
abstract: Neurofibromatosis type 1 (NF1) is a common inherited cancer predisposition syndrome. The NF1 gene product, neurofibromin, is hypothesized to function as a tumor suppressor and nearly all NF1 patients develop benign peripheral nerve tumors. These neurofibromas presumably arise from NF1 inactivation in S100(+)Schwann cells, but there is no formal proof for this mechanism. We demonstrate that fibro-blasts isolated from neurofibromas carried at least one normal NF1 allele and expressed both NF1 mRNA and protein, whereas the S100(+)cells typically lacked the NF1 transcript. Our findings further indicate that additional molecular events aside from NF1 inactivation in Schwann cells and/or other neural crest derivatives contribute to neurofibroma formation.
authors.affiliation: Departments of Neurology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104-4318, USA, jlr@mail.med.upenn.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Rutkowski
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: P J
authors.initials: PJ
authors.lastname: Boyer
authors.forename: E
authors.initials: E
authors.lastname: Legius
mesh_terms: D000328:Adult; D000483:Alleles; D015152:Blotting, Northern; D015153:Blotting, Western; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009432:Neural Crest / Q000378:metabolism; D009455:Neurofibroma / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism; D025542:Neurofibromin 1; D010641:Phenotype; D011506:Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
chemical_list: D025542:Neurofibromin 1; D011506:Proteins; D009418:S100 Proteins; D014404:Tubulin