Genomics Opens New Realms of Cancer Research

It took more than a decade of hard work at multiple research centers around the world to sequence the estimated 25,000 genes in the human genome. Bradley R. Cairns, PhD, Huntsman Cancer Institute (HCI) Senior Director of Basic Science and Co-Chair and Professor in the Department of Oncological Sciences at the University of Utah, remembers the early days of his own research before the human genome was sequenced—examining one gene at a time and laboriously teasing out information on how it worked over a period of weeks or months.

"What was beyond the scope of imagination five years ago is now routine at HCI," says Cairns. "Now you can look at every single gene in the human genome and its expression status at once, and the process takes only a few days."

Bradley Cairns, PhD

Genomics is the study of genes—the units that control the behavior of all cells in our bodies. Understanding the behavior of genes is essential to understanding cancer, because tumors are caused when genetic information goes haywire, changing the behavior of the gene so cells multiply out of control. HCI is on the leading edge in the field of genomics. Our cutting-edge genome sequencing equipment can survey a human genome in about a week. The speed and accuracy of this technology gives genomics many uses in cancer research—both in the lab and in the clinic.

The Potential to Change a Cancerous Cell Back to Normal

HCI researchers use genomics to find details of how a cancer cell functions compared to normal cells.

"The speed and depth with which new technology can produce genomic analysis makes it easier than ever before to quickly identify new genes that increase the risk of developing a specific cancer," says Cairns. "In some cases, there are gene mutations that on their own may have little effect on risk, but when they occur in combination with another gene mutation, there is a strong effect. The latest genomics technology allows us to identify these gene combinations much more readily than before." Watch the video about the potential of genomics.

Some cancers are the result of mutations or changes that cause genes to function abnormally. Some develop because a gene or combination of genes is missing from a person's genome. Other cancers occur because of molecular changes in the body that block or "silence" proper gene functioning. Studies of these mechanisms that surround the genes (called epigenetics) can lead to new approaches to cancer treatment.

"One order of business is to determine whether the gene is present—that's a genomics approach," says Cairns. "Second, is the gene there, but silenced due to a molecular change in the body? And third, can we turn the gene back on to get it functioning properly?

"Reactivating the silenced gene could change a cell back from being malignant or metastatic to a different state that can be treated more effectively. It could even change the cell back to normal," he adds.

Finding the Best Medicine for Each Individual

Another type of genomics study compares the genomes of cancer patients who are responding well to a particular chemotherapy with those of patients whose tumors don't respond to therapy. "With a study like this, researchers could find a signature set of genes that identify patients who will respond best to a particular type of chemotherapy.

"This kind of personalized medicine helps doctors decide the best treatment to give," says Cairns. "With this information, they can take a more focused approach to treatment and avoid the side effects and expense of drugs that are not likely to work well for that particular patient."

The personalized medicine made possible by genomic analysis can extend beyond cancer treatment to cancer prevention. Some HCI studies have already shown the way. HCI investigators Joshua Schiffman, MD, and Jared Rutter, PhD, worked together to identify a gene that increases the risk of a head and neck cancer called paraganglioma. (Read about this discovery in the 2009 and 2010 Annual Reports.) Next, using the Utah Population Database, researchers identified families that have a history of paraganglioma and arranged cancer screenings for family members at high risk of developing the tumor. The screenings revealed paraganglioma tumors in several of the individuals tested before any symptoms were even present. As a result, these individuals received treatment before the tumors became a major health problem.

"Now when a patient comes into the clinic with this type of cancer, we recognize that there's a high probability the gene is carried in the family," says Cairns. "We can encourage other members of the family to get genetic testing to help predict whether they are susceptible, get them on a screening plan, and give them early treatment if necessary."

Utah's Important Advantages

"Utah has a major advantage in genomics studies because of the Utah Population Database (UPDB)," Cairns says. "Because of its enormous size and depth, the UPDB allows geneticists here to show with high statistical probability that a gene that increases risk for cancer actually runs through a family." Read more about the UPDB.

Cairns also credits the solid partnership between faculty members designing studies to answer important genomics questions and the "talented and dedicated people" in HCI's shared resources: Microarray and Genomic Analysis (MGA), which performs the sequencing, the Bioinformatics Shared Resource (a separate section of the MGA), which provides the detailed analyses required to interpret the massive data produced by genome sequencing, and Research Informatics, which provides the database and computing infrastructure for the other two shared resources.

"At a cancer institute, one of the big purposes is to translate basic science into clinical medicine. With our expertise in cancer genetics and now the technology to analyze a genome, HCI is the perfect place to do that," says Cairns.