REDUCED EXPRESSION OF NEUROFIBROMIN IN THE SOFT-TISSUE TUMORS OBTAINED FROM PATIENTS WITH NEUROFIBROMATOSIS TYPE-1

1. We analysed the expression of neurofibromin mRNAs, encoded by the g ene responsible for neurofibromatosis type 1, and of neurofibromin pro tein in nine soft tissue tumours by S1 nuclease mapping and Western bl ot analyses. Four tumours were obtained from patients with neurofibrom atosis type 1, comprising two neurofibromas, one fibrolipoma and one m alignant schwannoma, and five neurogenic tumours were obtained from no n-neurofibromatosis type 1 patients. 2. All tumours, except for a mali gnant schwannoma, similarly expressed three species of mRNA encoding n eurofibromin, an isoform with the insertion of 21 amino acids in the d omain related to ras GTPase-activating protein, and an N-terminal isof orm lacking this domain. 3. Western blot analysis demonstrated deficie ncy of neurofibromin in the tumours derived from three out of the four neurofibromatosis type 1 patients: a fibrolipoma, a malignant schwann oma and a neurofibroma. In contrast, reduction in neurofibromin was no t detected in the five tumours obtained from non-neurofibromatosis typ e 1 patients. Furthermore, the expression of uas GTPase-activating pro tein was detected in all nine tumours examined. 4. The undetectable or reduced level of neurofibromin in the tumours obtained from neurofibr omatosis type 1 patients suggests that this deficiency is closely rela ted to their tumourigenesis.