Sequence of the FRA3B common fragile region: implications for the mechanism of FHIT deletion.

Inoue, H; Ishii, H; Alder, H; Snyder, E; Druck, T; Huebner, K; Croce, C M · Proc Natl Acad Sci U S A · 1997

basic_science · Level V

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Abstract

The hypothesis that chromosomal fragile sites may be "weak links" that result in hot spots for cancer-specific chromosome rearrangements was supported by the discovery that numerous cancer cell homozygous deletions and a familial translocation map within the FHIT gene, which encompasses the common fragile site, FRA3B. Sequence analysis of 276 kb of the FRA3B/FHIT locus and 22 associated cancer cell deletion endpoints shows that this locus is a frequent target of homologous recombination between long interspersed nuclear element sequences resulting in FHIT gene internal deletions, probably as a result of carcinogen-induced damage at FRA3B fragile sites.

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