The breakage-fusion-bridge (BFB) cycles in chromosome 17 create the gradient of copy-number increases for ERBB2 amplification (model). (A) A break at the telomeric side of the ERBB2 gene can initiate the BFB cycles and can result in ERBB2 amplification. Genomic segments harboring the ERBB2 gene are shown in red; the flanking centromeric segment is shown in yellow; and a telomeric fragment is shown in blue. In this figure, the initiating break between the blue and the white segments leads to a series of chromatid fusions and inverted duplications (centers shown in yellow triangles) that results in a chromosome with the amplified ERBB2 gene (star). (B) The BFB cycles can result in the gradient of copy-number increases on an array-CGH platform. Illustrated are a normal cell with two normal chromosomes and a tumor cell with a chromosome generated by the BFB cycles (star in A) and a normal chromosome. An array-CGH experiment for measuring relative copy number (tumor/normal) shows the gradient of copy-number increase toward the ERBB2 gene in the tumor cell (right). Red arrow, the copy-number transition that marks the initiating region of ERBB2 amplification.