Double trouble: Cells with duplicate genomes can trigger tumors

So-called “double-value” cells are produced by random errors in cell division that occur with unknown frequency. The generation of these genetically unstable cells appears to be a “pathway for generating a tumor,” says David Pellman, MD, a pediatric oncologist at Dana-Farber and at Children’s Hospital Boston and an associate professor at Harvard Medical School. He is the senior author on a report in the Oct. 13, 2005 issue of Nature. Takeshi Fujiwara, PhD, and Madhavi Bandi of Dana-Farber are the paper’s co-first authors.

The research was performed in experimental animals, but such “double-value” cells are seen in a variety of early human cancers and in a precancerous condition called Barrett’s esophagus. In addition to the extra chromosomes, the “double value” or “tetraploid” cells also duplicate a cell structure called the centrosome that plays a role in maintaining a stable genome. The extra centrosomes may be at the root of the cancer- triggering process. Once the genetic instability sets in, tumors “evolve” by losing, gaining and rearranging chromosomes.

The new findings confirm a far-sighted notion of Theodor Boveri, a German scientist of the 19th century who was one of the discoverers that the chromosomes in the nucleus of the cell carry the material of heredity, or genes. In 1914, he published what Pellman calls an “amazingly accurate and prescient” treatise suggesting, among other things, that genetic instability was a cause of malignant tumors.