Breakages at common fragile sites set boundaries of amplified regions in two leukemia cell lines K562 - Molecular characterization of FRA2H and localization of a new CFS FRA2S.

Abstract Genome amplification is often observed in human tumors. The breakage–fusion–bridge (BFB) cycle is the mechanism that often underlies duplicated regions. Some research has indicated common fragile sites (CFS) as possible sites of chromosome breakages at the origin of BFB cycles. Here we searched two human genome regions known as amplification hot spots for any DNA copy number amplifications by analyzing 21 cancer cell lines to investigate the relationship between genomic fragility and amplification. We identified a duplicated region on a chromosomes der(2) present in the karyotype of two analysed leukemia cell lines K562. The two duplicated regions are organized into large palindromes, which suggests that one BFB cycle has occurred. Our findings show that the three breakpoints are localized in the sequence of three CFSs: FRA2H (2q32.1–q32.2), which here has been characterized molecularly; FRA2S (2q22.3–q23.3), a newly localized aphidicolin inducible CFS; and FRA2G (2q24.3–q31).