From its beginning, Huntsman Cancer Institute (HCI) has expressed the research ideal of “from the lab bench to the patient bedside.” HCI investigators worked across disciplines in 2009 to find a gene mutation that causes an inherited head and neck cancer predisposition—and use it to help patients within six months of the discovery.

Although scientists have marked and labeled the entire human genome and the genomes of many other species, they do not yet know the function of many genes. Jared Rutter, PhD, associate professor of biochemistry at the University of Utah School of Medicine and a member of HCI’s Nuclear Control of Cell Growth and Differentiation Program, chose to study one such gene, called SDH5.

“It appears in essentially all organisms, even down to yeast,” Rutter says. “We decided it must be doing something important, or it wouldn’t be in all these species.”

Joshua Schiffman, MD, and Jared Rutter, PhD

Rutter and his laboratory team found SDH5 to be part of a gene complex controlling the way cells convert food into energy the body can use. Mutations in this complex cause excess glucose, the simple form of sugar that powers the cells, and additional blood vessels—both conditions involved in tumor formation. Three other genes in the complex had already been associated with various forms (or syndromes) of an inherited predisposition for a cancer called paraganglioma (PGL).

A fourth PGL syndrome existed for which the underlying gene had not been identified. Rutter’s team worked with another HCI investigator, pediatric oncologist Joshua Schiffman, MD, and data from a family with this syndrome to find that members of the family who developed PGL carried the same mutation to the SDH5 gene, thus identifying the unknown gene mutation.

Schiffman is a member of the Cancer Control and Population Sciences Program and medical director of the High Risk Pediatric Cancer Clinic (HRPCC) at HCI, in cooperation with Primary Children’s Medical Center. The HRPCC is part of the Family Cancer Assessment Clinic, one of HCI’s High Risk Cancer Clinics. In the HRPCC, Schiffman works with a large Utah family that carries one of the three previously known inherited PGL syndromes. What resulted was a strategic collaboration of a PhD doing basic science and an MD working to care for patients.

What’s important about this new gene discovery? Previous genetic tests could identify mutations in only about 70% of people suspected of having inherited PGL syndromes. Now tests for the SDH5 gene are used, increasing the percentage of patients whose underlying mutation can be identified.

Schiffman explains how young children in families with these predispositions really benefit. “We know the earliest tumors can form at around 10 years of age. You need to start screening these kids early and frequently—but screening doesn’t make sense unless you know what you’re looking for,” says Schiffman.

Identifying people in need of special cancer screening is the most immediate purpose of this gene discovery. But, says Schiffman, knowing the underlying genetic mutation and how it allows tumors to form will also be essential in finding targeted therapies for PGL and possibly other cancers.

“We’re in a really good position to learn as much as we can from these families, put that data together with the laboratory science, and translate it into amazing advances,” says Schiffman. “By virtue of HCI being so focused on genetic research, the resources available, the patient population, and its reputation, we’re very well poised to make this a clinically useful discovery and translate it directly to patients.”

Brandon Bentz, MD, assistant professor in the Department of Surgery at the University of Utah School of Medicine and an HCI investigator, co-authored the article in which the SDH5 gene discovery was reported. Rutter and Schiffman continue research into other genes involved in causing PGL.