Allelic loss at the neurofibromatosis type 1 (NF1) gene locus is frequent in desmoplastic neurotropic melanoma

Mutations of the tumour-suppressor gene NFI (neurofibromatosis 1) have been observed in neurofibromas and neurofibrosarcomas of patients with von Reck linghausen's disease and in sporadic nerve sheath tumours. In contrast, mel anoma, another tumour type of neuroectodermal origin, rarely shows NF1 alte rations. Desmoplastic neurotropic melanoma (DNM) is an uncommon melanoma su btype that shares morphological characteristics with nerve sheath tumours. Therefore, we analysed 15 DNM and 20 melanomas without morphological featur es of desmoplasia or neuroid differentiation (common melanomas) for loss of heterozygosity (LOH) at the NFI locus and flanking regions. Allelic loss w as detected in 10/15 (67%) DNM but only in 1/20 (5%) common melanomas. LOH was most frequently observed at marker IVS38, located in intron 38 of NFI. These data suggest a role for NFI in the pathogenesis of DNM and support an earlier hypothesis that exon 37 might encode a functional domain, DNM may represent an interesting tumour model for the further elucidation of the ce llular functions and tumour-suppressive potential of neurofibromin.