Mayo Clinic researchers have produced the first laboratory evidence to show that a cell's possession of an abnormal number of chromosomes contributes to the development of cancers. Their report on the role of this chromosomal instability, known as aneuploidy, appears in the Journal of Cell Biology.

Because 85 percent of human cancer cells possess an abnormal number of chromosomes, researchers have long been curious about the role of aneuploidy in the multistep cancer process. Questions centering on the role of aneuploidy have been regarded as classics in cancer biology-questions such as: Does chromosomal instability play a functional role that is necessary for cancers to grow? Or, is it merely a feature of cancerous growth?

The achievement of the Mayo Clinic study is that it provides laboratory proof from animal studies supporting a theory that researchers around the world have held for several years. As such, the Mayo team found a clear correlation between the development of cancer and defects in the "mitotic checkpoint"-a cellular mechanism that, when working properly, works like a security system to guard against abnormal numbers of chromosomes being distributed to cells.

"We actually find clear correlations now between the susceptibility to cancer and the rate at which chromosomal instability occurs in the cell," says Jan Van Deursen, Ph.D., a Mayo Clinic research scientist and principal investigator of the study. "It really confirms what everybody always suspected, but was unable to show experimentally."

First described just five years ago, the mitotic checkpoint is still being elaborated - and one part of the Mayo study discovers a new component of it. The mitotic checkpoint is thought to consist of at least 10-15 components that function like a molecular security system for the orderly progression through the cell growth cycle. In humans, that means every healthy cell must have 46 chromosomes.

"If you don't have this checkpoint on the highest alert at all times, you start to make mistakes," says Van Deursen. In some cancer cells, there may be 60 or even 80 chromosomes instead of 46.

Think of aneuploidy as causing chromosomal instability. This state of being out of balance leads to a cascading effect in which low-level expression of one protein inside a cell produces an abnormal number of chromosomes and more instability. This instability, in turn, creates the vulnerability to cancers.

SOURCES:
Journal of Cell Biology, online edition, February 3, 2003
Mayo Clinic (http://www.mayo.edu)