Spontaneous chromosomal aberrations in cell cultures from patients with neurofibromatosis 1

Neurofibroma-derived cell cultures, skin fibroblast strains from NF1 patients, melanocyte cultures from café-au-lait spots and melanocytes from skin overlying neurofibroma were investigated with regard to the frequencies of spontaneous chromosomal aberrations. A 3.4-fold increased rate of stable and unstable chromosome aberrations in 34 neurofibroma cultures of 18 NF1 patients was noticed in comparison to 17 skin biopsy-derived cultures of healthy probands. Fibroblast strains from the unaffected skin of nine NF1 patients revealed a 2.6-fold higher rate of chromosome breakage compared with the control cultures. Likewise, an increase of spontaneous chromosomal instability by a factor of 13.5 was found in cultured melanocytes from café-au-lait spots and by a factor of 11.9 in the skin-melanocyte cultures of six NF1 patients in comparison to foreskin-derived melanocyte strains of five unaffected persons. Analyses of the distribution of chromatid and chromosome breaks along the chromosomes revealed a significant clustering of these events in the centromeric regions specifically in the four kinds of NF1-derived cultures.