A case of elevated spontaneous micronucleus frequency derived from chromosome 2

This work tested the hypothesis that the content of spontaneous micronuclei in lymphocytes in an apparently healthy normal human subject, who exhibite d an unusually high micronucleus frequency, was non-random. Several DNA pro bes were used in fluorescent in-situ hybridization (FISH), beginning with a probe generated from the subject's micronuclei. Micronuclei obtained from peripheral blood lymphocytes by microdissection were subjected to random am plification of polymorphic DNA (RAPD-PCR), and a unique PCR product was the n used to isolate a cosmid clone from a human genomic library. This clone h ybridized to chromosome 2. Subsequently, commercial probes were included in FISH analyses of micronuclei from the subject and age- and sex-matched con trols. No significant differences were found between subject and controls i n the percentages of micronuclei hybridizing with a centromere probe for th e X chromosome or a painting probe for chromosome 3. However, the subject h ad a very highly significant increase (p < 0.0001) in chromosome 2 in micro nuclei over a level that might be expected to be present by chance. Charact erization of micronuclei may be a promising tool in studies of mechanisms o f inherited or induced chromosome instability. The strength of the strategy employed in this study is that, by characterizing the chromosomes present in micronuclei, this work has advanced from an observation of chromosomal i nstability to a foundation for study of the mechanism underlying the observ ation. (C) 1999 Elsevier Science B.V. All rights reserved.