Molecular Characterization Informs Prognosis in Patients With Localized Ewing Sarcoma: A Report From the Children’s Oncology Group
This study looks to identify subgroups within localized Ewing sarcoma (EWS) that are associated with treatment response or resistance. The investigators analyzed clinical and molecular traits from 351 patients with localized EWS. DNA sequencing was performed to identify common EWS gene fusions, changes in the number of copies of specific segments of DNA in the genome called recurrent copy number alterations (CNAs), and mutations in two different proteins called TP53 and STAG2. EWS fusions were identified in 282 (80.3%) patients. Pathogenic TP53 mutations were identified in 14 of 277 (5.1%) patients and STAG2 mutations in 21 of 277 (7.6%) patients. A total of 63.1% of patients were found to have recurrent CNAs. Upon analysis, patients with TP53 mutation had an increased incidence of relapse (5-year cumulative incidence of relapse of 43%) compared to patients without TP53 mutation (22%), STAG2 mutations had in increase in relapse (53%) compared to those without (21%), as did patients with recurrent CNAs (30%) compared to those without (16%). When analysis was performed on multiple characteristics at the same time, STAG2 mutation was the only molecular biomarker that remained prognostic. These results indicate that localized EWS patients with STAG mutations are a high-risk population and treatment strategies may need to take this into account.