Grant: Operating Grant

Alveolar rhabdomyosarcoma (aRMS) is an aggressive cancer that afflicts children and adolescents. The predominant cause of this childhood cancer is the production of a new gene, which results from DNA damage in the cell. Here, breaks in DNA strands lead to the fusion of two distinct genes, producing a new version that imparts tremendous growth capacity to cells, leading to the formation of an aggressive tumor. Despite the lethality of this form of cancer, little information is available regarding the mechanism that promotes the initial DNA damage, the exact cell type in which this event occurs, and how this abnormal gene acts to create a cancer cell. Here, we will test the hypothesis that the initial cancer fusion gene is produced during the normal maturation process in mature muscle cells, converting them to a cancer "stem cell state". In addition, we will identify the genes that are activated by this fused gene and the factors that interact with this fused gene to promote tumor cell growth, key information that will be required for the development of new treatment strategies to treat aRMS patients.