How do tumors make ends meet?

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Abstract
When Barbara McClintock irradiated strains of Indian corn in the early 30s, she identified ring chromosomes, which she soon realized were a special case of chromosomes broken by radiation; the broken ends sometimes fused to one another and formed a ring (1, 2). This discovery led McClintock to hypothesize the existence of a special structure at the chromosome tip that would maintain chromosome stability. In 1941 she described the breakage-fusion-bridge cycle, a model for a repeating pattern of chromosome behavior that is triggered by an initial breakage (3). Normally, each chromatid strand has one centromere, and the chromosome ends remain capped by the telomeres that protect the ends from sticking to one another. But sometimes, harmful substances or radiation damage a chromatid and cause it to break. Without telomere caps, the new ends stick to each other, and the resulting fused chromosome has two centromeres as well as a duplication of some of the genes from that chromosome. When cell division occurs, the two centromeres of this unusual chromosome may be pulled to the opposite spindle poles of the cell, forming an irregular, long chromosome bridge between the two newly forming daughter cells (Fig. 1 A and B). Eventually, the abnormal chromatid breaks in two or may be left behind during cell division. If the chromosome ends are broken, they are likely to rejoin again, reforming a chromosome bridge at the next division. Anaphase bridges. (A and B) Images from the late 1930s show Indian corn chromosomes that have duplicated and separated. A “chromatin bridge” connects one chromosome from the upper set to one from the lower set (ref. 53; reproduced courtesy of B. McClintock and the American Philosophical Society Library). (C) Chromosome spread prepared from pistils of a late-generation telomerase-deficient mustard weed mutant. End-to-end chromosome fusions are …