SEQUENCE OF THE FRA3B COMMON FRAGILE REGION - IMPLICATIONS FOR THE MECHANISM OF FHIT DELETION

The hypothesis that chromosomal fragile sites may be ''weak links'' th at result in hot spots for cancer-specific chromosome rearrangements w as supported by the discovery that numerous cancer cell homozygous del etions and a familial translocation map within the FHIT gene, which en compasses the common fragile site, FRA3B. Sequence analysis of 276 kb of the FRA3B/FHIT locus and 22 associated cancer cell deletion endpoin ts shows that this locus is a frequent target of homologous recombinat ion between long interspersed nuclear element sequences resulting in F HIT gene internal deletions, probably as a result of carcinogen-induce d damage at FRA3B fragile sites.