Thursday, August 22, 2019


"Sleeping Beauty" DNA helps researchers identify cancer genes
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Dr. David Largaespada and his team of cancer researchers have discovered a fast way to identify cancer-causing genes. (Photo courtesy of the University of Minnesota)
University of Minnesota researchers have discovered a way to quickly identify cancer-causing genes in mice. They hope the discovery will help other scientists come up with new cancer therapies for humans. Up until now, finding cancer genes has been like looking for a needle in a haystack. But U of M scientists say they've hastened the search process by programming a piece of DNA they call "Sleeping Beauty."

Minneapolis, Minn. — The "Sleeping Beauty" DNA is unique for two reasons. First, the DNA is highly mobile and jumps easily from one gene to the next. It's also dormant.

It also has been asleep in mammals and other organisms for millions of years. It's essentially a piece of junk DNA that simply wasn't useful.

But Sleeping Beauty isn't asleep anymore.

A few years ago, U of M scientist Perry Hackett figured out how to re-activate the jumping DNA in mice. The discovery was important, because jumping genes offer scientists a fast, simple way to manipulate other genes to figure out how they work -- and why in some cases, they become defective.

One of Hackett's colleagues, cancer researcher David Largaespada, remembers the moment he first saw Hackett's research paper back in 1997.

"I immediately thought, 'This could be used as a gene identification tool for mouse genetics,'" says Largaespada. "And I knew one application would be to find cancer genes."

Largaespada got to work on a project of his own. He bred Hackett's mice containing the newly-awakened jumping DNA, with another group of mice that had a special tumor-igniting protein. Then he waited as the jumping DNA went to work in the offspring, hopping randomly from gene to gene.

Whenever the jumping DNA would come in contact with a cancer-causing gene, Largaespada says a tumor would begin to grow in that spot.

We know we're on the right track because many of the genes that we found in our initial work are known human cancer genes. So that gives us proof of principle.
- Dr. David Largaespada

"And that gives us a flag planted there. It says, 'This is a cancer gene,'" says Largaespada.

There's a lot of similarity between how cancer develops in mice and how it develops in humans, according to Largaespada. He was able to test out his theory by comparing his mouse tumor results with a list of about 300 known human cancers.

"We know we're on the right track, because many of the genes that we found in our initial work are known human cancer genes. So that gives us proof of principle," says Largaespada.

Every time U of M researchers find a new mouse tumor, they will first determine whether it's one of the known cancer genes. If it isn't, Largaespada says they will add it to a list of newly identified cancer genes that other scientists can then study further.

Largaespada estimates there are hundreds, perhaps even 1,000 or more, cancer-causing genes that haven't been discovered yet.

"The reason we need to know about all these genes is that cancer is basically a genetically-based disease. In order to treat it effectively, we need to develop therapies that target the specific mutant genes and the proteins they produce," says Largaespada. "And so in the absence of that information, we don't know where to start."

This additional genetic information will be particularly useful for chemists who are trying to come up with new cancer-fighting drugs. It's also possible that scientists will discover there are already drugs on the market for other diseases that could be effective in fighting some types of cancer.

Largaespada says the technique also makes it possible for researchers to conduct in-depth studies of specific types of cancer. At his lab, scientists are concentrating on learning more about prostate, lung and colorectal cancers.

But no matter what researchers focus on, Largaespada says the most important aspect of this recent discovery is that it buys them precious time in the war on cancer.

"This is giving us a shortcut, or a jump forward, in our ability to look at what are the really important genes in the mammalian genome that could be involved in cancer," he says.

Largaespada predicts that within four to five years researchers will have identified most, if not all, cancer-causing genes in humans, using the Sleeping Beauty and jumping DNA technique.

The study is published in the latest edition of the journal "Nature."