Monosomy 6 in human cultured fibroblast-like cells after long-term stimulation with acidic fibroblast growth factor (FGF1).
Long-term exposure to fibroblast growth factor type 1 (FGF1) of fibroblast-like cells derived from neurofibromas of patients with neurofibromatosis type 1, from angiofibromas of patients with tuberous sclerosis, and from foreskin of unaffected donors resulted in the outgrowth of monosomy 6 in 7 out of 14 cell lines examined. After their initial detection by cytogenetic analysis, the proportion of cells which had lost one chromosome 6 was monitored by FISH using a-satellite probes specific for chromosome 6 and 7, and by PCR analysis of polymorphic microsatellite markers. Monosomy 6 exceeding baseline levels developed only in cultures exposed to FGF 1, and the emergence of monosomic cells could not be correlated with a given donor's genotype. During serial culture, the proportion of monosomic cells increased to over 90% in 5 of the 7 affected strains. A conspicuous change of cellular morphology from spindle-shaped to more epithelial-type cells was noted in monosomic cultures, even though none of them converted to a permanent cell line during the observation period. We conclude that long-term exposure of human fibroblast-like cell strains to FGF1 results in the emergence of monosomy 6 in 50% of the cultures so treated. A selective advantage for such monosomic cells is the most likely explanation for their steady increase during serial culture.
Krone
W
W
Abteilung Humangenetik, Universität Ulm, Germany. winfrid.krone@medizin.uni-ulm.de
Kehrer-Sawatzki
H
H
Siegel
A
A
Röck
H
H
Götz
H
H
D000328:Adult; D002648:Child; D002896:Chromosomes, Human, Pair 6; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005347:Fibroblasts / Q000648:ultrastructure*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009455:Neurofibroma / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016220:Fibroblast Growth Factor 1