SPONTANEOUS CHROMOSOMAL-ABERRATIONS IN CELL-CULTURES FROM PATIENTS WITH NEUROFIBROMATOSIS-1

Neurofibroma-derived cell cultures, skin fibroblast strains from NF1 p atients, melanocyte cultures from cafe-au-lait spots and melanocytes f rom skin overlying neurofibroma were investigated with regard to the f requencies of spontaneous chromosomal aberrations. A 3.4-fold increase d rate of stable and unstable chromosome aberrations in 34 neurofibrom a cultures of 18 NF1 patients was noticed in comparison to 17 skin bio psy-derived cultures of healthy probands. Fibroblast strains from the unaffected skin of nine NF1 patients revealed a 2.6-fold higher rate o f chromosome breakage compared with the control cultures. Likewise, an increase of spontaneous chromosomal instability by a factor of 13.5 w as found in cultured melanocytes from cafe-au-lait spots and by a fact or of 11.9 in the skin-melanocyte cultures of six NF1 patients in comp arison to foreskin-derived melanocyte strains of five unaffected perso ns. Analyses of the distribution of chromatid and chromosome breaks al ong the chromosomes revealed a significant clustering of these events in the centromeric regions specifically in the four kinds of NF1-deriv ed cultures.