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| Home > Publications database > Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. |
| Home > Publications database > Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. |
| Journal Article | DKFZ-2025-02517 |
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2025
Academic Press
Orlando, Fla.
Abstract: Ewing sarcoma is a rare and aggressive tumor affecting mainly adolescents and young adults. Accurate risk stratification is critical for treatment tailoring, yet traditional clinical parameters lack sufficient predictive accuracy. While retrospective studies have identified potential molecular biomarkers, prospective validation is required for clinical implementation.The international PROVABES consortium (PROspective Validation of Biomarkers in Ewing Sarcoma) aims to evaluate molecular prognostic markers in European patients treated under international phase III trials. This study focuses on copy number alterations (CNAs), in 305 primary tumors. Tissue microarrays were analyzed by FISH for chromosome 1q gain (n = 297) and 16q loss (n = 266). Genome-wide CNAs were further assessed using SNP arrays in 139 samples. Associations with clinical outcomes were evaluated via Kaplan-Meier and multivariate Cox regression, with event-free survival (EFS) and overall survival (OS) as endpoints.Chromosome 1q gain was significantly associated with shorter OS in both localized cases and the overall cohort, and with inferior EFS specifically in localized patients. In contrast, 16q loss showed no significant prognostic impact. Multivariate analysis confirmed 1q gain as an independent predictor of poor EFS in localized disease. Notably, a higher fraction of genome altered was associated with inferior OS and EFS not only in localized patients but also in the entire cohort, and remained an independent predictor of outcome despite the smaller subset analyzed.This prospective study validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. Furthermore, the extent of genomic alteration emerges as a promising predictor of both OS and EFS. Incorporating these biomarkers may improve individualized risk stratification and ultimately enhance patient outcomes.
Keyword(s): Chromosome 1q gain ; Copy number alterations ; Ewing sarcoma ; Prognostic biomarker ; Prospective validation
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