Examining the link between chromosomal instability and aneuploidy in human cells

SL Thompson, DA Compton - The Journal of cell biology, 2008 - rupress.org
SL Thompson, DA Compton
The Journal of cell biology, 2008rupress.org
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 …
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.
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