The presence of this hot spot might explain why the frequency of recombination for a gene is higher when it is located closer to HER2 and gradually decreases for genes located far away from HER2. In general, the gene amplification architectures derived from our results illustrate the complexity of the rearrangement mechanisms (sister chromatid breakage-fusion-bridge cycles, formation and reinsertion of double minutes and repeated units at a single locus) and highlight the diversity of HER2-amplified cancers [40,41]. The gene discussed is ERBB2; the disease is cancer.