THE GUANINE TRIPHOSPHATASE (GTPASE) ACTIVATING PROTEIN (GAP)-RELATED DOMAIN OF THE NEUROFIBROMATOSIS TYPE-1 GENE IS NOT MUTATED IN NEURAL CREST-DERIVED SPORADIC TUMORS

We conducted a mutation analysis of the most conserved region of the n eurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase ) activating protein (GAP)-related domain (NF1 GRD), to which the func tion of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the l ikelihood of finding structural alterations resulting in loss of funct ion of this region in tumours of neuroepithelial tissues, where the ac tivity of neurofibromin seems to be crucial in regulating the mechanis ms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were i dentified in the tumours analysed. We conclude that the loss of NF1 ge ne tumour suppressor function, that might lead or contribute to the de velopment of malignancies in neuroectodermal tissues, is not due to st ructural abnormalities of the region of the gene which interacts with p21 ras. (C) 1998 Elsevier Science Ltd. All rights reserved.