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Published online February 18, 2008
doi:10.1083/jcb.200712029
The Journal of Cell Biology, Vol. 180, No. 4, 665-672
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Thompson et al.
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 Examining the link between chromosomal instability and aneuploidy in human cells

Sarah L. Thompson and Duane A. Compton

Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755

Correspondence to Duane A. Compton: duane.a.compton{at}dartmouth.edu

Solid tumors can be highly aneuploid and many display high rates of chromosome missegregation in a phenomenon called chromosomal instability (CIN). In principle, aneuploidy is the consequence of CIN, but the relationship between CIN and aneuploidy has not been clearly defined. In this study, we use live cell imaging and clonal cell analyses to evaluate the fidelity of chromosome segregation in chromosomally stable and unstable human cells. We show that improper microtubule–chromosome attachment (merotely) is a cause of chromosome missegregation in unstable cells and that increasing chromosome missegregation rates by elevating merotely during consecutive mitoses generates CIN in otherwise stable, near-diploid cells. However, chromosome missegregation compromises the proliferation of diploid cells, indicating that phenotypic changes that permit the propagation of nondiploid cells must combine with elevated chromosome missegregation rates to generate aneuploid cells with CIN.

Abbreviation used in this paper: CIN, chromosomal instability.


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