TP53 MUTATIONS ARE FREQUENT IN MALIGNANT NFI TUMORS

Neurofibromatosis type I (NF1) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. Th e NF1 gene has been cloned and maps to 17q 11.2, and the gene product acts as a tumor suppressor gene. Here we analyzed the role of mutation s in TP53 in four malignant NF1 tumors. Mutations were found in 3 out of 4 tumors. One Of these mutations is a common missense mutation in c odon 278 in one of the previously identified hot spots for mutations. The two other are hitherto unreported mutations, including a splice mu tation of exon 3 and a nonsense mutation in exon 4. In addition, these four tumors also showed loss of heterozygosity (LOH) for markers on c hromosome 17 in the region of TP53. Malignant NF1 tumors are initiated by a somatic inactivation of the second NF1 allele. Tumor progression , however, occurs by accumulation of additional genetic abnormalities, such as homozygous inactivation of TP53, as demonstrated in this pape r. Genes Chromosom Cancer 10:250-255 (1994). (C) 1994 Wiley-Liss, Inc.