Chromosome instability in lymphocytes from two patients affected by three sequential primary cancers: The role of fragile sites

The chromosomal aberration rate and the expression of fragile sites induced by aphidicolin were evaluated in metaphase chromosomes obtained from perip heral blood lymphocytes of two untreated patients with multiple primary can cers. Spontaneous aberrations of chromosome number and structure and chromo some fragility were compared with controls with the use of the same methods . Chromosomal aberration rates and expression frequencies of fragile sites were significantly higher in the patients than in normal control subjects. In the patients, all but one structural chromosome aberration involved at l east one fragile site. Our results suggest that fragile sites may be unstab le regions of the human genome, which might play an important role in the g enetic instability associated with cancer predisposition. (C) Elsevier Scie nce Inc., 1999. All rights reserved.