Jpn J Clin Oncol. 2025 Nov 9:hyaf174. doi: 10.1093/jjco/hyaf174. Online ahead of print.
ABSTRACT
BACKGROUND: Ewing sarcoma (ES) is a malignant type of bone and soft tissue tumor with EWSR1-ETS gene fusions as the primary driver alteration. Incidence is higher in White populations compared to Black and Asian populations. Researchers use next-generation sequencing to identify alterations as potential therapeutic targets. We compared the data from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets in the USA with the data from Center for Cancer Genomics and Advanced Therapeutics in Japan.
METHODS: We sequenced tumor DNA from 81 ES samples using the FoundationOne® CDx for multigene panel testing. Genetic alterations were interpreted via the Cancer Knowledge Database (CKDB) and potentially actionable alterations were classified into levels A-F.
RESULTS: Analysis of 81 ES samples revealed 556 mutations in 197 genes and 126 copy-number alterations in 58 genes. Potentially actionable alterations were detected in 10 patients (12.3%) at CKDB levels A or C. STAG2 mutations accounted for 3.7%, TP53 mutations for 17.3%, and CDKN2A deletions for 13.6%. There was no significant difference in overall survival after genomic profiling test enrollment for STAG2 and TP53 mutations (P = .663 and P = .767), but those with CDKN2A and CDKN2B deletions had poor prognosis (P = .024 and P = .012).
CONCLUSION: Compared to previous reports, Japanese ES cases showed lower STAG2 and higher TP53 mutation frequencies. CDKN2A and CDKN2B deletions may serve as prognostic biomarkers indicating unfavorable outcomes.
PMID:41206913 | DOI:10.1093/jjco/hyaf174
