MOLECULAR ANALYSIS OF THE NF2 TUMOR-SUPPRESSOR GENE IN SCHWANNOMATOSIS

Patients with multiple schwannomas without vestibular schwannomas have been postulated to compose a distinct subclass of neurofibromatosis ( NF), termed ''schwannomatosis.'' To compare the molecular-genetic basi s of schwannomatosis with NF2, we examined the NF2 locus in 20 unrelat ed schwannomatosis patients and their affected relatives. Tumors from these patients frequently harbored typical truncating mutations of the NF2 gene and loss of heterozygosity of the surrounding region of chro mosome 22, Surprisingly, unlike patients with NF2, no heterozygous NF2 -gene changes were seen in normal tissues. Examination of multiple tum ors from the same patient revealed that some schwannomatosis patients are somatic mosaics for NF2-gene changes. By contrast, other individua ls, particularly those with a positive family history, appear to have an inherited predisposition to formation of tumors that carry somatic alterations of the NF2 gene. Further work is needed to define the path ogenetics of this unusual disease mechanism.