A chromosome (blue) whose kinetochore (green) is attached to spindle microtubules (red) from both poles lags behind during mitosis and creates aneuploidy.

Cancer cells need a little something extra to propagate with unusual chromosome numbers, based on evidence from Thompson and Compton.

Many tumors are packed with cells that have too many or too few chromosomes—a state known as aneuploidy. In theory, aneuploidy is the result of chromosome segregation errors during mitosis. The authors now identify one mechanism behind these errors: anaphase starts up while chromosomes are wrongly attached to both poles.

For proper segregation, sister chromatids of each chromosome should attach to opposite poles. But in several cancer cell lines, chromatids were often hitched to both poles during division, resulting in daughter cells with either both copies of a chromosome or neither.

Chromosome attachment is monitored by the spindle checkpoint, but this mechanism only stalls anaphase when it recognizes unattached chromosomes; it does not sense chromatid attachment to both poles. How they are prevented in normal cells is not yet known but probably involves microtubule detachment by aurora kinase.

Even with high segregation error rates, diploid cancer cell lines failed to maintain abnormal chromosome numbers. In two diploid lines, newly formed aneuploid cells were rapidly lost over subsequent generations. Perhaps aneuploid cells undergo apoptosis or senescence or are simply too slow-growing to compete with their diploid neighbors.

The authors now want to determine how aneuploid tumor cells keep their mismatched chromosome sets. Once their secret is identified, it might prove to be a therapeutic target that is unique to the tumor.


Thompson, S.L., and D.A. Compton.
J. Cell Biol.