Developmental window explains origin of non-muscle cell pediatric rhabdomyosarcoma

Rhabdomyosarcoma is the most common pediatric soft tissue carcinoma. It has a poor prognosis for high-risk disease, indicating a need for a better fundamental understanding of the cancer. The most common form, fusion-negative, appears to originate from muscle-related cells. However, more recent research has shown that endothelial-related cells can transform into the disease. This explained how the cancer occurs in nonmuscle tissues, though the cell type and process remained unclear.

A study led by Mark Hatley, MD, PhD, St. Jude Division of Molecular Oncology director and Department of Oncology associate member, found that only a specific subset of endothelial progenitor cells during a small window of embryonic developmental signaling can become fusion-negative rhabdomyosarcoma. That small window of vulnerability during development may explain why rhabdomyosarcoma is primarily a pediatric tumor and provide further insights into the signaling pathways that lead to oncogenic transformation. The findings were published in Cell Reports.

“The dogma has been that rhabdomyosarcoma arises from skeletal muscle stem cells; however, these cells are present and function throughout life — not explaining how the disease is largely restricted to children,” Hatley said. “Our work highlights how endothelial progenitor cells work in concert with specific signaling programs at defined developmental timepoints to restrict the formation of rhabdomyosarcoma to childhood.”

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