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OHSU Researchers Find Cause of Chromosomal Abnormalities in Cancer Cells

   Portland, Ore.

Findings may help physicians better diagnose and treat all cancers

Researchers at Oregon Health & Science University have achieved a better understanding of recurring chromosomal abnormalities that may help physicians better diagnose and treat virtually all types of human cancers. The investigators discovered that chromosomal aberrations found in some cancer cells cause significant delays in chromosome replication and other important cellular processes - delays thought to contribute to the unstable nature of cancer cells. Their conclusions will appear in the November 6 edition of the Proceedings of the National Academy of Sciences.

"One of the reasons cancers recur after a course of treatment is that the unstable nature of cancer cells make them prone to rapid changes," said Mathew Thayer, Ph.D., professor of molecular medicine in OHSU's School of Medicine and an author of the study. "If we can better understand the cellular processes that lead to instability, we may be able to intervene at some point in that process, in effect 'stabilizing' the cells and significantly reducing their ability to develop resistance."

Thayer and colleagues Leslie Smith and Annemieke Plug, Ph.D., report several distinguishing features of chromosomes with aberrations known as whole-arm translocations, in which segments from two different chromosomes exchange places. Some of the chromosomes that undergo this type of translocation show a significant delay in the compacting process that occurs in chromosomes at the onset of cell division. This delay appears to be caused by an earlier delay in the process of DNA replication. Both processes are linked to chromosomal instability.

A more stable cancer cell means that entire classes of anti-cancer drugs and therapies may work better, longer.

"Cancer cells tend to develop resistance not to a single drug or therapy but to all of them," said Thayer. "The great promise is that the reverse is also true - that finding ways to stabilize cancer cells will improve the effectiveness of all anti-cancer therapies."

To conduct this research, Thayer and colleagues employed a basic-science technique in which chromosomes are stained, compared and analyzed.

"It's good to be reminded that 21st century cancer research does not always require gene sequences and other high-technology equipment to make a contribution to scholarship," said Thayer.

The research was funded by the National Institutes of Health and was conducted under the auspices of the OHSU Cancer Institute. The institute strives to link basic science research to treatment and prevention of cancers, targeting the molecular basis of each disease.

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