Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an 
increased risk for developing benign and malignant tumors. The NFI gene has been 
cloned and maps to 17q11.2, and the gene product acts as a tumor suppressor 
gene. Here we analyzed the role of mutations in TP53 in four malignant NFI 
tumors. Mutations were found in 3 out of 4 tumors. One of these mutations is a 
common missense mutation in codon 278 in one of the previously identified hot 
spots for mutations. The two other are hitherto unreported mutations, including 
a splice mutation of exon 3 and a nonsense mutation in exon 4. In addition, 
these four tumors also showed loss of heterozygosity (LOH) for markers on 
chromosome 17 in the region of TP53. Malignant NFI tumors are initiated by a 
somatic inactivation of the second NFI allele. Tumor progression, however, 
occurs by accumulation of additional genetic abnormalities, such as homozygous 
inactivation of TP53, as demonstrated in this paper.