GENETIC ALTERATIONS IN A MALIGNANT SCHWANNOMA FROM A PATIENT WITH NEUROFIBROMATOSIS (NF1)

In a patient with neurofibromatosis (von Recklinghausen disease; NF1), normal lymphocytes, five cutaneous neurofibromas, and tumour tissue f rom a recurrence of a malignant schwannoma were analysed for genetic a lterations. Eleven DNA markers located on chromosome 17 and nine rando mly chosen markers representing chromosomes 1, 2, 3, 4, S, 6, and 11, were analysed. High resolution Giemsa banding of lymphocytes revealed no chromosomal rearrangement. The DNA from the neurofibromas were all found to have the same restricted fragment length polymorphism pattern as the constitutional DNA from the patient. In the malignant schwanno ma a complete loss of one allele was found at polymorphic loci on chro mosome arm 17p. One gene copy of the TP53 gene (17p13.1) and the NF1 g ene (17q11.2) was lost, as was one copy of the PGA gene (11q13). No mu tations were detected in the mutational hotspots of the TP53 gene. Par tial losses were detected at three loci on chromosomes 1,2 and 6, indi cating a clonal variation within the tumour since histological evaluat ion disclosed no normal tissue in the analysed specimen. Our data indi cate that the NF1 gene may function as a tumour suppressor gene, and t hat, either by effect of dose reduction or complete inactivation, both the NF1 gene and the TP53 gene may be critical for the progression of a neurofibroma to a malignant schwannoma. The observations made are c onsistent with the concept of stepwise multigenetic changes in tumour progression.