Funded by the Dick Vitale Pediatric Cancer Research Fund
Rhabdomyosarcoma is the most common childhood cancer. Its most hard-to-treat subtype, fusion-positive alveolar Rhabdomyosarcoma (FP-ARMS), is mainly caused by chromosome translocations that form a “fused oncogene” called PAX3-FOXO1 or PAX7-FOXO1. Although the genetic mutations leading to FP-ARMS has been known for decades, the effective therapy to treat FP-ARMS patients is still lacking: less than 50% of the patients are cured, and patients survival rate is less than 10%. In FP-ARMS translocation, a piece of DNA is “fused” to another piece of DNA. Such fused DNA sequence not only consists of the protein-coding genes but also of the non-coding DNA sequences. These non-coding sequences used to be called as “junk DNA”, but more and more studies have shown that they play essential roles in human diseases, including cancer. However, in FP-ARMS, we know very little about whether or how the “fused” non-coding DNA sequences contribute to cancer. In this study, we will take advantage the newly developed technology to address this question that has never been asked: how the “fused” non-coding DNA sequences contribute to tumor development. Our work will help to understand the mechanism that control FP-ARMS development, and in the future, to provide new drug targets for better therapies. More importantly, since chromosome translocation is frequently observed in many childhood cancer types, our pioneer work will also establish the new methods that can be applied to study other pediatric cancers.