Microsatellite instability and promoter methylation as possible causes of NF1 gene inactivation in neurofibromas

Neurofibromatosis type 1 (NF1) is a frequent hereditary disorder. One of th e characteristic features of this disease is the development of neurofibrom as. Since the NF1 gene is supposed to be a tumour suppressor gene, these ne urofibromas should develop upon inactivation of both NF1 alleles. So far, m utation and deletion have been found to be involved in NF1 gene inactivatio n. However, these inactivating mechanisms explain the development of only a limited fraction of analysed neurofibromas. In this study, we investigated microsatellite instability (MSI) and promoter methylation as potential con tributors to NF1 gene inactivation. As site-specific methylation in the NF1 promoter inhibits binding of transcription factors Spl and CREB, we studie d the methylation status of their binding sites in particular. We analysed 20 neurofibromas and three neurofibrosarcomas, but did not find evidence fo r microsatellite instability or NF1 promoter methylation in any of the tumo urs. Thus, our data suggest that both microsatellite instability and promot er methylation are unlikely to be the major causes of NF1 gene inactivation in these tumours.