Allelic loss of the NF1 gene in NF1-associated plexiform neurofibromas

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with a complex variety of clinical symptoms. Genetic alteration of the NF1 gene on 17q11.2 is the cause of this disease. Neurofibromas of the peripheral nervous syst em are one main manifestation. A variant of neurofibroma is the plexiform n eurofibroma which can be found in about 30% of NF1-patients, often causing severe clinical symptoms. In this study, we examined 14 such tumors from 10 NF1-patients for allele loss of the NF1 gene (LOH: loss of heterozygosity) using four intragenic polymorphic markers. Loss of heterozygosity was foun d in eight rumors from five patients, and suspected in one additional tumor from another patient. This finding suggests that loss of the second allele , and thus inactivation of both alleles of the NF1 gene, is associated with the development of plexiform neurofibromas. The 14 plexiform neufibromas w ere also examined for mutation in the TP53 gene by screening exons 5 throug h 8 using temperature gradient gel electrophoresis. No mutation was found i n any of the tumors. (C) Elsevier Science Inc., 1999. All rights reserved.