TP53 and MYOD1 variants are associated with more aggressive forms of rhabdomyosarcoma, a rare childhood cancer, and poorer outcomes, according to the results of the largest international genomic profiling study of the disease. The findings, which were published in the Journal of Clinical Oncology, have implications for somatic biomarker testing to guide tailored treatment approaches.

Using next-generation sequencing on tissues collected over two decades of clinical trials, researchers from the U.S. National Cancer Institute and the U.K. Institute for Cancer Research analyzed DNA from tumor samples from 641 children with rhabdomyosarcoma. They found that patients with variants in the tumor suppressor genes TP53MYOD1, or CDKN2A had a poorer prognosis than patients without those variants. Most patients had a median of one variant per tumor, but those with two or more variants per tumor had even poorer survival outcomes.

Previous studies have linked the PAX-FOXO1 fusion gene to poor outcomes from rhabdomyosarcoma. In the current study, more than 50% of patients without the PAX-FOXO1 fusion gene had RAS pathway variants, although they were not associated with survival outcomes.  

Identifying a cancer’s genomic characteristics can help clinicians predict treatment response and help scientists focus on specific targets for future therapies. More research is needed, but germline and somatic biomarker testing “is going to become the standard of care,” the authors said. “Instead of just the pathologists looking at these tumors, we’re now going to have molecular profiling, and that’s a leap forward.”