Neurofibromatosis type I (NF1) is an autosomal dominant disorder affecting 1 in 
3000 people. The NF1 gene is located on chromosome 17q11.2, spans 350 kb of 
genomic DNA, and contains 60 exons. A major phenotypic feature of the disease is 
the widespread occurrence of benign dermal and plexiform neurofibromas. Genetic 
and biochemical data support the hypothesis that NF1 acts as a tumour suppressor 
gene. Molecular analysis of a number of NF1 specific tumours has shown the 
inactivation of both NF1 alleles during tumourigenesis, in accordance with 
Knudson's "two hit" hypothesis. We have studied 82 tumours from 45 NF1 patients. 
Two separate strategies were used in this study to search for the somatic 
changes involved in the formation of NF1 tumours. First, evidence of loss of 
heterozygosity (LOH) of the NF1 gene region was investigated, and, second, a 
screen for the presence of sequence alterations was conducted on a large panel 
of DNA derived from matched blood/tumour pairs. In this study, the largest of 
its kind to date, we found that 12% of the tumours (10/82) exhibited LOH; 
previous studies have detected LOH in 3-36% of the neurofibromas examined. In 
addition, an SSCP/HA mutation screen identified five novel NF1 germline and two 
somatic mutations. In a plexiform neurofibroma from an NF1 patient, mutations in 
both NF1 alleles have been characterised.