Understanding a Rare Cancer in Duchenne Muscular Dystrophy Patients

Muscle stem cells can contribute to a specific, rare cancer in patients with Duchenne muscular dystrophy (DMD), according to a new report.

The muscle cancer is called rhabdomyosarcoma (RMS), a rare soft tissue sarcoma that can develop throughout life, but which has a higher incidence in young children.

Since DMD induces increased skeletal muscle regeneration, the incidence of a tumor is increased. The condition primarily affects boys with typical onset between the ages of 3 and 5 years old. The study authors noted that due to recent medical advances, children with DMD are surviving their teenage years into their 30s, but there is still a need for effective treatments.

Investigators from Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, tested multiple types of cells, including fibroadipogenic progenitors (FAPs) in order to understand how RMS develops in DMD patients. They used a mouse model of severe DMD to test the stem cells. These FAPs are key players in DMD progression, the study authors told Rare Disease Report®.

The mice with more severe DMD developed RSM sooner. The investigators then isolated cells responsible for muscular regeneration from the severe DMD mice and observed their ability to form tumors. The stem cells formed tumors independently, while the other cells did not. The muscle stem cells also indicated they would develop into tumors showing DNA damage and gene expression patterns observed in human RSM.

“We were struck by how strong the tumor formation effect was for the muscle stem cells. It was very clear that muscle stem cells developed into tumors, but not other cells,” senior author Alessandra Sacco, PhD, said. “This indicates there is a specific pressure on the muscle stem cell compartment that can lead to tumor formation, and identifying the cancer cell of origin is a crucial step towards the development of potential treatments.”

The investigators identified 2 genes linked to the tumor growth called Ccl11 and Rgs5. They are typically activated in inflammation and wound healing. When the investigators added Ccl11 and Rgs5 to tumor cells, it reduced their growth. They hypothesized that these genes therefore were involved in the growth of the cancer.

According to Sacco, these findings are the first step in developing effective treatments for RMS in DMD patients.

“This study is important for scientists, including ourselves, who are working to treat DMD by stimulating muscle stem cell growth,” she said. “These findings indicate that efforts to target muscle stem cells should take into account potential cancer risk in this chronic degenerative disease. To be successful, these approaches will need to find the right balance between promoting muscle stem cell-mediated tissue repair while avoiding potential transformation.”

The investigators noted that RMS in DMD is not well studied, adding that there are only 4 case reports. It will take time before the team’s findings can influence and change clinical practice.

“This is partially because only now have medical advances enabled to extend life expectancy for people with DMD,” Sacco said. “But now that we know this could occur, doctors and scientists should track cancer incidence in DMD so we know more concretely how often and when during disease progression this can occur in patients.”

The paper, titled “Muscle Stem Cells Can Drive Cancer That Arises in Duchenne Muscular Dystrophy,” was published in the journal Cell Reports.