RAS-GTP LEVELS ARE ELEVATED IN HUMAN NF1 PERIPHERAL-NERVE TUMORS

Neurofibromin, the gene product of NF1, is a Pas GTPase Activating Pro tein. The absence of neurofibromin leads to increased levels of Ras-GT P, which contributes to the proliferation of NF1 neurogenic sarcoma ce ll lines. Whether this pathogenic mechanism is applicable to benign an d malignant peripheral nerve tumours from NF1 and non NF1 patients is not known, due to lack of a tissue based assay, We have adapted a colo rimetric enzymatic assay for determining levels of Pas bound guanine n ucleotides in tissues, Ras-GTP levels were increased in NF1 neurogenic sarcomas (15 times) and benign NF1 neurofibromas (four times), compar ed to non NF1 schwannomas. Neurofibromin was not expressed in NF1 sarc omas, in support of its important negative Ras regulatory role in the pathogenesis of NF1 peripheral nerve tumors.