ALTERATIONS AT CHROMOSOME-17 LOCI IN PERIPHERAL-NERVE SHEATH TUMORS

Little is known about the molecular genetic changes in malignant perip heral nerve sheath tumors (MPNST). Inactivation of the TP53 gene in 17 p has been reported in a few tumors. The MPNST is one of the manifesta tions of neurofibromatosis 1 (NF1), suggesting that the NF1 gene in 17 q might be important. We present a study of 15 neurofibromas and MPNST from nine individuals. Seven patients had NF1, and six of these devel oped MPNST. Genetic alterations at nine polymorphic loci on chromosome 17 were examined. Allelic imbalance was detected only in the malignan t tumors from NF1 patients (4/6). Complete loss of heterozygosity of 1 7q loci was found in three of these tumors, all including loci within the NF1 gene. Two of the malignant tumors also showed deletions on 17p . No mutations were detected within exon 5-8 of the TP53 in any of the MPNST, and none of them were TP53 protein-positive using immunostaini ng with mono- and polyclonal antibodies against TP53. The numbers of c hromosome 17 present in each tumor were evaluated by use of fluorescen ce in situ hybridization (FISH) on interphase nuclei with a centromere -specific probe. A deviation from the disomic status of chromosome 17 was observed in two of the MPNST from NF1 patients. These results supp ort the hypothesis of inactivation of both NF1 gene alleles during dev elopment of MPNST in patients with NF1. In contrast to other reports, we did not find evidence for a homozygous mutated condition of the TP5 3 gene in the same tumors. Finally, FISH analysis was in accordance wi th the DNA analysis in the deduction of the numbers of chromosome 17 i n these tumors.