Chromosomal complications

By Tia Ghose

Courtesy of Beth A. Weaver

The paper:

B.A. Weaver et al., "Aneuploidy acts both oncogenically and as a tumor suppressor," Cancer Cell, 11:25–36. (Cited in 70 papers)

The finding:

Beth Ann Weaver, a cell biologist at the University of Wisconsin–Madison, showed that mice with lower levels of centromere protein E (CENP-E), a motor protein that sorts chromosomes during mitosis, had higher rates of abnormal chromosome numbers, or aneuploidy. CENP-E–deficient mice also had more spleen and lung tumors but, surprisingly, had fewer liver tumors.

The controversy:

Weaver's group claimed that aneuploidy was the sole culprit in altered tumor formation rates, but CENP-E might have other effects, too, says Robert Benezra of Memorial Sloan-Kettering Cancer Center. "You can never be sure that you are only inducing aneuploidy," he says. The Mayo Clinic's Jan van Deursen agrees: "The claim that this is the best model for aneuploidy...

The look back:

The findings spurred van Deursen and others to reanalyze older studies for a link between tumor suppression and aneuploidy. For example, data from New York Medical College's Wei Dai indicated that aneuploidy also suppressed cancer of the small intestine (PNAS, 102:4365–70, 2005).

The step forward:

Weaver's lab is currently testing the hypothesis that lower rates of aneuploidy drive cancer, while higher rates cause cell death and therefore suppress cancer.


Percentage of mice with cancer
Cocktail Spleen tumor Liver tumor
Wild type: 0% 14%
CENP-E deficient: 10% 7%

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