U. team zeroes in on childhood cancer

University of Utah researchers have successfully created a deadly fast-moving form of childhood cancer in mice — a step they hope will one day lead to effective treatments.

It's the first time a mouse model has been created for aveolar rhabdomyosarcoma, a deadly form of cancer that affects muscle and which few children survive.

Creating the model has reversed some of the thinking about how the disease occurs, said lead investigator Mario Capecchi, co-chairman of human genetics in the U. School of Medicine and an investigator with the Howard Hughes Medical Institute. Two new studies are being published back to back in the next issue of Genes and Development. The first shows what a fusion gene does and the second how to generate the tumor in mice.

Capecchi called the disease a "very mean form of cancer," despite aggressive treatment. While treatments for many other cancers have improved greatly, there has been little change in survival rates for children with this cancer over the past 30 years.

"Cancer is never the result of one event," said Capecchi. The U. researchers based their efforts on the realization that "most cancers don't originate at conception. You don't get them from your mother or father. They show up in somatic tissue, which is all tissue but germ cells, usually after birth."

Muscles form in two ways. In an embryo's early development there are cells that run up and down the body, creating the patterns the muscle will occupy in the adult. And after birth, muscles are also made from satellite cells, which are capable of dividing themselves and also of differentiating to form muscle. That's what adds bulk to muscle, he said. Those satellite cells also help replace muscle broken down by exercise, he said.

Scientists have suspected that those satellite stem cells that become new muscle lead to the disease. The U. research suggests instead that the cancer begins in more mature skeletal muscle fiber.

While childhood cancer is rare, the American Cancer Society says that 9,200 cases will be diagnosed in children under age 14 this year. Of those, 313 will be rhabdomyosarcomas, of which the aveolar variety is just one type.

Only 5 to 30 percent of children with that form of cancer survive five years.