Benign neurofibromas in type 1 neurofibromatosis (NF1) show somatic deletions of the NF1 gene.

Neurofibromatosis type 1 (NF1) is one of the most common human autosomal dominant diseases. NF1 is characterized by café-au-lait spots (CLS), axillary freckles and Lisch nodules of the iris. Another hallmark of NF1 is the development of neurofibromas, benign tumours that arise from peripheral nerve sheaths. NF1 patients also have an increased incidence of certain malignant tumours. Malignancies in NF1 are believed to follow the 'two-hit' hypothesis, in which one allele is constitutionally inactivated while the other allele is subsequently inactivated ('second hit') at the somatic level. This hypothesis has not, however, been fully tested in the aetiology of benign neurofibromas. This is a crucial issue since it addresses not only the basic mechanism behind the genesis of neurofibromas, but may also indicate a mechanism common to many or all NF1 features. Using both NF1 intragenic polymorphisms as well as markers from flanking and more distal regions of chromosome 17, we have investigated loss of heterozygosity (LOH) in 22 neurofibromas from five unrelated NF1 patients. Eight of these tumours revealed somatic deletions involving NF1, indicating that inactivation of NF1 is associated with at least some neurofibromas.