Reduced Expression of Neurofibromin in the Soft Tissue Tumours Obtained from Patients with Neurofibromatosis Type 1

1. We analysed the expression of neurofibromin mRNAs, encoded by the gene responsible for neurofibromatosis type 1, and of neurofibromin protein in nine soft tissue tumours by S1 nuclease mapping and Western blot analyses. Four tumours were obtained from patients with neurofibromatosis type 1, comprising two neurofibromas, one fibrolipoma and one malignant schwannoma, and five neurogenic tumours were obtained from non-neurofibromatosis type 1 patients. 2. All tumours, except for a malignant schwannoma, similarly expressed three species of mRNA encoding neurofibromin, an isoform with the insertion of 21 amino acids in the domain related to ras GTPase-activating protein, and an N-terminal isoform lacking this domain. 3. Western blot analysis demonstrated deficiency of neurofibromin in the tumours derived from three out of the four neurofibromatosis type 1 patients: a fibrolipoma, a malignant schwannoma and a neurofibroma. In contrast, reduction in neurofibromin was not detected in the five tumours obtained from non-neurofibromatosis type 1 patients. Furthermore, the expression of ras GTPase-activating protein was detected in all nine tumours examined. 4. The undetectable or reduced level of neurofibromin in the tumours obtained from neurofibromatosis type 1 patients suggests that this deficiency is closely related to their tumourigenesis.