10:16am Friday 13 December 2019

How "Sleeping Beauty" is Helping Researchers Understand Cancer

As development occurs, the genes encoded by our genome act in an orchestrated manner to give us the traits we possess – like brown hair or blue eyes. Our genomes consist of DNA molecules which contain two strands, interwoven in a double helix in a particular arrangement, that possess all of the biological information that our bodies need to develop.

Remarkably, there are pieces of DNA that can move to a different location in that arrangement. These portable elements of DNA sequence, called transposons, can sometimes cause changes to our genomes that potentially lead to a wide variety of diseases, including cancer. Scientists aren’t sure why transposons exist in the first place, but it’s possible that these elements, by moving from place to place in DNA, may also create some beneficial diversity in the body.

Lara Collier, PhD, a UW Carbone Cancer Center scientist, utilizes a certain transposable element as a tool to study which genes may play a roll in cancer formation. About 20 years ago, scientists came upon a particularly potent string of transposons in fish that had become dormant and incapable of moving to new places in the genome. Known as “Sleeping Beauty,” this DNA sequence was then brought back to life in the lab. The result was an awakened element of DNA that can cause big changes in how genes are expressed – and help Collier identify genes that are involved in cancer formation.

Collier and her team engineer the Sleeping Beauty transposon into healthy cells in mice, then allow the transposons to mobilize and cause genetic changes that eventually lead to tumor formation. Candidate cancer genes are identified by finding DNA that transposons have inserted into the tumor.

By comparing what comes up in their experiments to gene mutations that occur in patients with specific cancers, Collier and her team have begun focusing their studies on genes that they believe drive tumor formation when mutated. They are now studying the normal actions of these genes during development and also how their abnormal function may contribute to cancer formation.

“Cancer doesn’t occur just because of one genetic change but a combination of changes,” explains Collier. “The key is finding out exactly which combination of genetic changes lead to tumors, and how these changes cause cells to become abnormal in the first place.”

“Think of how many cells we have in our body,” she adds. “It’s amazing to think of how they know to become what they are and stay normal. I want to find out when happens when things don’t go according to plan and how we can utilize that information to better treat cancer.”

University of Wisconsin Hospitals and Clinics Authority

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