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Mitotic Cell Death by Chromosome Fragmentation

¹ Center for Molecular Medicine and Genetics, ² Department of Pathology, ³ Karmanos Cancer Institute, ⁴ Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan; ⁵ SeeDNA Biotech, Inc., Windsor, Ontario, Canada; and ⁶ Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan

Requests for reprints: Henry H.Q. Heng, Wayne State University School of Medicine, Room 3226, 540 East Canfield, Detroit, MI 48201. Phone: 313-577-9544; Fax: 313-577-6200; E-mail: hheng{at}med.wayne.edu.

Cell death plays a key role for both cancer progression and treatment. In this report, we characterize chromosome fragmentation, a new type of cell death that takes place during metaphase where condensed chromosomes are progressively degraded. It occurs spontaneously without any treatment in instances such as inherited status of genomic instability, or it can be induced by treatment with chemotherapeutics. It is observed within cell lines, tumors, and lymphocytes of cancer patients. The process of chromosome fragmentation results in loss of viability, but is apparently nonapoptotic and further differs from cellular death defined by mitotic catastrophe. Chromosome fragmentation represents an efficient means of induced cell death and is a clinically relevant biomarker of mitotic cell death. Chromosome fragmentation serves as a method to eliminate genomically unstable cells. Paradoxically, this process could result in genome aberrations common in cancer. The characterization of chromosome fragmentation may also shine light on the mechanism of chromosomal pulverization. [Cancer Res 2007;67(16):7686–94]