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Aneuploidy: Instigator and Inhibitor of Tumorigenesis

Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California

Requests for reprints: Don W. Cleveland, Ludwig Institute for Cancer Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0670. Phone: 858-534-7811; Fax: 858-534-7659; E-mail: dcleveland{at}ucsd.edu.

Aneuploidy, an aberrant chromosome number, has been recognized as a common characteristic of cancer cells for more than 100 years and has been suggested as a cause of tumorigenesis for nearly as long. However, this proposal had remained untested due to the difficulty of selectively generating aneuploidy without causing other damage. Using Cenp-E heterozygous animals, which develop whole chromosome aneuploidy in the absence of other defects, we have found that aneuploidy promotes tumorigenesis in some contexts and inhibits it in others. These findings confirm that aneuploidy can act oncogenically and reveal a previously unsuspected role for aneuploidy as a tumor suppressor. [Cancer Res 2007;67(21):10103–5]

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