Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines

Qinghua Shi and Randall W. King ()
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Qinghua Shi: Harvard Medical School
Randall W. King: Harvard Medical School

Nature, 2005, vol. 437, issue 7061, 1038-1042

Abstract: Cancer and cell division A hypothesis about cancer initiation, first proposed nearly a century ago, has stood the test of time. German biologist Theodor Boveri suggested that a failure of cell division might produce tetraploid cells (containing a double chromosome quota) that then undergo multipolar mitosis, leading to genome instability that can trigger cancer. Fujiwara et al. tested the hypothesis using an actin inhibitor to block cell division and generate tetraploid cells. The resulting cells can be transformed in vitro and also generate tumours in mice. The transformed cells exhibit massive genomic instability, including an amplification of a region containing genes associated with breast cancers. A second study shows that accurate chromosome segregation is coupled to the completion of cytokinesis in human cells. It had been assumed that if a pair of chromosomes failed to separate during cell division, two aneuploid daughter cells (not containing a multiple of the haploid chromosome number) would form. Instead, mitosis is halted and tetraploid cells are produced at least initially. This mechanism may explain why the loss or gain of a single chromosome is relatively rare in cancers and it may help prevent some cancers though tetraploid cells are, as Boveri suggested, also prone to forming cancers.

Date: 2005
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DOI: 10.1038/nature03958

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