MINNEAPOLIS / ST.PAUL (Dec. 29, 2006) —University of Minnesota cancer researchers have discovered that an inherited mutation in a DNA replication gene may increase breast cancer risk.

Naoko Shima, Ph.D., an assistant professor and researcher with the University of Minnesota Medical School and Cancer Center, led the laboratory team that made this discovery in mice. Their findings are published in the Dec. 27, 2006, issue of the journal Nature Genetics.

Shima and her colleagues initially found a mutant line of mice called Chaos3 that exhibits a high rate of spontaneous chromosome aberrations. They then discovered that the Chaos3 mice carry a subtle mutation in a gene called Mcm4.

The Mcm4 gene encodes one of six related Mcm proteins whose purpose in the body is copying DNA (DNA replication). The identified genetic abnormality appears to impair the DNA replication process that exclusively leads to the formation of mammary tumor in nearly all of the female mutant mice.

Mcm proteins are extensively studied as a cancer marker, because cancer cells retain a higher level of Mcm proteins than normal cells.

"Our discovery demonstrates for the first time a link between an inherited mutation in a Mcm gene and breast cancer predisposition," Shima said. "This discovery may provide an important clue to understanding the genetic mechanism of developing breast cancer, because Mcm genes have not previously been linked with breast cancer. What our discovery potentially means is that women who are found to have a similar abnormal genetic change in Mcm genes may also be predisposed to getting breast cancer."

The next steps in this research will include investigating the mechanisms of why mutant Mcm4 mice are prone to developing mammary tumors and corroborating the laboratory finding in humans.

Shima worked with the following researchers on this study: Ana Alcaraz, Ivan Liachko, Robert Munroe, Suzanne Hartford, Bik Tye, and John Schimenti, all of Cornell University, and Tavanna Buske and Catherine Andrews of the University of Minnesota.

This research work was supported by grants from the National Institutes of Health to Schimenti, and a Department of Defense grant to Shima.

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Media Contact:

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