What does a gene that's been dormant in salmon for 15 million years have to do with cancer? Plenty.

Eight years ago, University of Minnesota researcher Perry Hackett, Ph.D., found a way to reawaken the inactive gene in salmon. He named the gene Sleeping Beauty. Scientists classify Sleeping Beauty as a transposon; informally, it's called a jumping gene because of its ability to jump from one location on the chromosome, or piece of DNA, to another. Hackett's finding prompted scientists around the world to begin exploring Sleeping Beauty's potential as a taxicab for transporting other useful genes into an organism's genetic material.

This year, researchers at the University of Minnesota Cancer Center and the National Cancer Institute (NCI) reported a new and exciting use for Sleeping Beauty — helping to find genes that, when altered, contribute to the development of cancer.

"Cancer develops as a consequence of mutations or changes that occur in a rare cell in our body," says David Largaespada, Ph.D., associate professor of genetics, cell biology and development. Largaespada headed the Cancer Center portion of the study and collaborated on the NCI work.

"We need to know for each and every kind of human cancer, which genes can become mutated," he says. "The reason thats important is that once such genes have been identified, researchers can get to work finding ways to tailormake drugs or other treatments that target these genes to fight that type of cancer."

To find genes that, when altered, stimulate the development of cancer, the Cancer Center and NCI researchers modified the Sleeping Beauty transposon to contain bits of DNA that can activate or inactivate gene transcription — the process by which the cell takes information from genes to make proteins. The researchers placed the modified transposon components in the genomes of mice, then crossed those mice with others bred to be particularly susceptible to cancer. When the offspring mice developed various types of cancer, the researchers took a micro-look at the genes of the cancer cells. By observing where Sleeping Beauty had inserted itself, the researchers could identify genes in which mutation — in this case caused by the Sleeping Beauty transposon — resulted in the development of cancer.

"We need to know for each and every kind of human cancer, which genes can become mutated. The reason that's important is that once such genes have been identified, researchers can get to work finding ways to tailor-make drugs or other treatments that target these genes to fight that type of cancer."
— David Largaespada, Ph.D.

"What we're able to get from these mouse tumors is a cancer genetic fingerprint for each type of tumor," Largaespada says.

In this newest research, the Cancer Center team focused on finding genes linked to the development of solid tumors called sarcomas. The NCI team used Sleeping Beauty to explore genes related to immune system cancers known as lymphomas.

The Sleeping Beauty transposon illustrates how basic research — scientific activity aimed at understanding the fundamental hows and whys of biology — is the starting point that can lead to new and better ways of preventing, diagnosing and treating disease. The transposon was originally revived from millennia-long slumber to give researchers a tool for genetically modifying fish. Researchers now anticipate it could be used to identify cancer genes in any type of tissue. That information could then be applied to developing and refining drugs to treat solid tumors. Information provided by observing the effect of the transposon could also offer insights into whether a gene acts alone or with others ininfluencing the development of cancer — insights that could prove useful in treating the disease.

"It shows the importance of basic work, doing the kinds of studies that may not have an immediately obvious application," Largaespada says. "Studying fish transposons is kind of fringe research."

Largaespada's team is now planning to use Sleeping Beauty to pinpoint genes related to prostate, lung and colorectal cancer. The team that published the companion paper, led by NCI researchers Nancy Jenkins, Ph.D., and Neal Copeland, Ph.D., will focus on finding the locations of genes that contribute to brain cancer, melanoma, leukemia and lymphoma.

Largaespada anticipates thatthe information gained from the Sleeping Beauty studies could be used for detecting cancer earlier and treating it more effectively in about five years.

"Because cancer is a genetically based disease, finding these genes really tells us what the weak points are so we can attack them," he says.

The two research studies about the use of Sleeping Beauty ,to more accurately and efficiently find cancer-causing genes were published in the prestigious science journal, Nature. Cancer Center researchers Lara Collier, Ph.D., and Corey Carlson, Ph.D., worked with Largaespada on this research.

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This story was originally published in the University of Minnesota Cancer Center 2005 Annual Report.