U of M's Cancer Researcher Investigates Mysterious Tumor Disorder in Children

MINNEAPOLIS/ST. PAUL (Dec. 4, 2008) -- David Largaespada, Ph.D., scientist and professor with the University of Minnesota’s Masonic Cancer Center and Medical School, has been awarded a nearly $800,000 grant as part of a collaboration with researchers at Cincinnati Children’s Hospital, Cincinnati, Ohio, to study NF1 syndrome, a genetic disorder that, among other problems, causes benign tumors to grow in the nerves. These benign tumors, called neurofibromas, can sometimes suddenly transform into a malignant state, called malignant peripheral nerve sheath tumor (MPNST).

The National Institute of Neurological Disorders and Stroke (NINDS), a unit of the National Institutes of Health in Washington, D.C., awarded the grant.

Largaespada leads the Masonic Cancer Center’s Genetic Mechanisms of Cancer Research Program. With his share of the award – totaling $792,095 over five years –Largaespada will use an innovative technique, called Sleeping Beauty mutagenesis, to conduct laboratory research focusing on screening for genes that lead to MPNST. His goal will be to identify the genetic change that causes these malignant tumors so that more effective treatments can be developed to help NF1 patients in this situation.

The genetic disorder is known as neurofibromatosis type 1.  It is a complex disease that results in a variety of medical problems, including benign, and sometimes malignant, tumors of the nervous system. The disorder affects about one in 3,500 to 4,000 people, and the reasons for NF1 remain largely unknown. Many people inherit this disorder, however, between 30 and 50 percent of new cases occur because of a spontaneous change in the NF1 gene, occurring either in the egg or sperm cells prior to conception or early in the person’s life. Once this genetic change occurs, the changed or mutated NF1 gene can be passed on to the next generation.

“The NF1 disorder most often becomes apparent by the time a child is 10 years old,” Largaespada said. “The tumors begin and often remain as benign growths. They can be surgically removed but often grow back. The symptoms are often mild and most children grow into adults and live long, productive lives.

“However, in about 3 to 5 percent of the affected patients, the tumors turn malignant and then they can be lethal,” Largaespada said.

Sleeping Beauty mutagenesis is a gene identification method discovered by laboratory researchers at the University of Minnesota. It involves using pieces of jumping genes, or transposons, that insert themselves into or between genes and can activate or deactivate a gene’s normal function.

“We want to identify genes that lie in the signaling pathways that interact with the NF1 disorder to cause MPNST,” Largaespada said. “This information can be used to develop drugs that target those genes and stop them from becoming malignant or treat them once they become malignant.”

The Masonic Cancer Center, University of Minnesota is part of the University’s Academic Health Center and designated by the National Cancer Institute as a Comprehensive Cancer Center for cancer research, treatment and education. For more information, visit www.cancer.umn.edu or call 612-624-2620.

Contact:          
Mary Lawson, Masonic Cancer Center, 612-624-6165 or mlawson@umn.edu
Emily Jensen, Academic Health Center, 612-624-9163 or jense888@umn.edu