Germline and Somatic Genetic Landscape of Pediatric Rhabdomyosarcoma

Overall Project Strategy: The objective of this project is to advance our understanding of the relationship between cancer predisposition genes and pediatric RMS. Our central hypotheses are: 1) mutations in cancer predisposition genes are more common than expected in children with RMS; and 2) children with fusion-negative tumors have a higher burden of germline mutations than those with fusion-positive tumors. The framework for this study relies on >600 well annotated samples collected from newly diagnosed RMS patients and stored in the Children’s Oncology Group (COG) Biopathology Center.]]>
Inclusion criteria:•    Documented diagnosis of rhabdomyosarcoma•    Males and females•    No ethnic or race restrictionsExclusion criteria•    Lack of consent•    Age at diagnosis >25 years]]>
Compared to other pediatric cancers, the outlook for children with rhabdomyosarcoma (RMS) remains poor. In particular, for those with high-risk disease, fewer than 43% of patients survive for more than 5 years. Currently, there are no genetic testing and counseling strategies for children with RMS; there are no clinical surveillance or prevention protocols; and there are few therapeutic targets for this highly fatal tumor. One of the strongest risk factors for RMS is having a genetic cancer predisposition syndrome. While it is believed that about 7% of RMS patients have changes (or mutations) in the genes responsible for these syndromes, there have been no population-based assessments to support this estimate. Because of this, we will leverage the resources of the Children’s Oncology Group, which is supported by the National Cancer Institute and has more than 200 participating institutions throughout the United States and Canada, to obtain over 600 samples from children newly diagnosed with RMS.]]>