Neurofibroma is a benign tumor that arises from small or large nerves. This 
neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of 
the most common autosomal dominant disorders. The NF1 gene codes for a protein 
called "neurofibromin." It possesses a region that shares a high homology with 
the family of GTPase-activating proteins, which are negative regulators of RAS 
function and thereby control cell growth and differentiation. The evidence 
points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an 
increased incidence of certain malignant tumors that are believed to follow the 
"two hit" hypothesis, with one allele constitutionally inactivated and the other 
somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been 
described for neurofibromas, and mutations in both copies of the NF1 gene have 
been reported for a dermal neurofibroma. The aim of our study was the analysis 
of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH 
analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family 
history of the disease and 8 of them sporadic. We have analyzed five intragenic 
NF1 markers and six extragenic markers, and we have found LOH in 25% of the 
neurofibromas (corresponding to 53% of the patients). In addition, we found that 
in the neurofibromas of patients from familial cases the deletions occurred in 
the allele that is not transmitted with the disease, indicating that both copies 
of the NF1 gene were inactivated in these tumors. Therefore, the recent reports 
mentioned above, together with our findings, strongly support the double 
inactivation of the NF1 gene in benign neurofibromas.