Alternative mechanisms of gene amplification in human cancers

Gene amplification is a common phenomenon in cancer. Cytogenetic analyses have indicated that breakage‐fusion‐bridge (BFB) cycles drive intrachromosomal amplification of some oncogenes in a head‐to‐head manner in human cancers. However, the complex structures of an amplified sequence found in cancers are not always explained by the BFB model. At the 17q21 locus, which is not linked to common fragile sites, we discovered a recombination hot spot harboring amplicon repeats in tandem in a head‐to‐tail orientation, with the interamplicon junctions in each cancer cell being homogeneous. These findings clearly show the presence of alternative mechanisms other than BFB cycles in oncogene amplification. © 2004 Wiley‐Liss, Inc.