APHIDICOLIN-INDUCED FRA3B BREAKPOINTS CLUSTER IN 2 DISTINCT REGIONS

The common fragile site at chromosomal band 3p14.2 (FRA3B) is the most sensitive single site in the human genome to induced chromosomal lesi ons. This fragile site may predispose chromosome 3p to breakage that i s commonly observed in lung, renal, and many other cancers, We previou sly used aphidicolin induction of FRA3B expression in a chromosome S-o nly somatic cell hybrid to generate a series of hybrids with breakpoin ts in the 3p14.2 region. These breakpoints were localized to two disti nct clusters, separated by 200 kb, that lie on either side of a region of frequent breakage within FRA3B as observed by FISH analysis. Seven proximal aphidicolin-induced breakpoints were localized at or near th e end of a THE element. The THE-1 element is flanked by LINE and Alu r epetitive elements. The eight distal aphidicolin-induced breakpoints c lustered in a region capable of forming multiple hairpin-like structur es, Thus repetitive elements and hairpin-like structures may be respon sible for chromosome fragility in this region. (C) 1997 Academic Press .