Spontaneous breakage and fragile site expression in chronic lymphocytic leukemia.
It has been suggested that genetic predisposition to cancer might be related to spontaneous chromosome instability or to fragile site expression. Therefore, spontaneous breakage and fragile sites were analyzed in nine untreated chronic lymphocytic leukemia (CLL) patients to determine their relation to cancer rearrangements. Five cases presented spontaneous gaps and breaks with a random distribution of breakpoints. In cultures treated with fluorodeoxyuridine or aphidicolin, 29 specific bands could be defined as fragile sites. A significant clustering of these sites was found with known common fragile sites (c-fra) and cancer breakpoints described in the literature. Most of these cancer breakpoints were involved in structural abnormalities associated with CLL (p < 0.00001). These data suggest that the expression of specific fragile sites might be related to structural chromosomal aberrations in CLL.
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Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Argentina.
Giere
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Larripa
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Slavutsky
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D000368:Aged; D016590:Aphidicolin; D019457:Chromosome Breakage / Q000235:genetics*; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002874:Chromosome Mapping; D005260:Female; D005467:Floxuridine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D005467:Floxuridine; D016590:Aphidicolin