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Updated: Mar 22, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Molecular Heterogeneity of Ewing Sarcoma as Detected by Ion Torrent Sequencing
Nana Zhang1,2, Haijing Liu1,2, Guanjun Yue1,2
1Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Abstract:
Ewing sarcoma (ES) is the second most common malignant bone and soft tissue tumor in children and adolescents. Despite advances in comprehensive treatment, patients with ES metastases still suffer poor outcomes, thus, emphasizing the need for detailed genetic profiles of ES patients to identify suitable molecular biomarkers for improved prognosis and development of effective and targeted therapies. In this study, the next generation sequencing Ion AmpliSeq™ Cancer Hotspot Panel v2 was used to identify cancer-related gene mutations in the tissue samples from 20 ES patients. This platform targeted 207 amplicons of 2800 loci in 50 cancer-related genes. Among the 20 tissue specimens, 62 nonsynonymous hotspot mutations were identified in 26 cancer-related genes, revealing the molecular heterogeneity of ES. Among these, five novel mutations in cancer-related genes (KDR, STK11, MLH1, KRAS, and PTPN11) were detected in ES, and these mutations were confirmed with traditional Sanger sequencing. ES patients with KDR, STK11, and MLH1 mutations had higher Ki-67 proliferation indices than the ES patients lacking such mutations. Notably, more than half of the ES patients harbored one or two possible 'druggable' mutations that have been previously linked to a clinical cancer treatment option. Our results provided the foundation to not only elucidate possible mechanisms involved in ES pathogenesis but also indicated the utility of Ion Torrent sequencing as a sensitive and cost-effective tool to screen key oncogenes and tumor suppressors in order to develop personalized therapy for ES patients.
Insights
Genetic profiling of Ewing sarcoma (ES) reveals mutations in key cancer genes. Next-generation sequencing identified novel mutations and druggable targets, paving the way for personalized therapies in this rare pediatric cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Ewing sarcoma (ES) is a rare but aggressive pediatric bone and soft tissue cancer.
- Current treatments for metastatic ES have limited efficacy, highlighting the need for novel therapeutic strategies.
- Detailed genetic characterization of ES is crucial for identifying biomarkers and developing targeted therapies.
Purpose of the Study:
- To identify cancer-related gene mutations in ES patients using next-generation sequencing.
- To explore the molecular heterogeneity of ES and discover potential therapeutic targets.
- To evaluate the utility of Ion Torrent sequencing for personalized medicine in ES.
Main Methods:
- Tissue samples from 20 ES patients were analyzed using the Ion AmpliSeq™ Cancer Hotspot Panel v2.
- This panel targeted 2,800 loci across 50 cancer-related genes.
- Identified mutations were confirmed using Sanger sequencing.
Main Results:
- Sixty-two nonsynonymous hotspot mutations were detected in 26 cancer-related genes across 20 ES specimens.
- Five novel mutations in KDR, STK11, MLH1, KRAS, and PTPN11 were identified.
- Mutations in KDR, STK11, and MLH1 correlated with higher Ki-67 proliferation indices.
- Over half of the patients harbored potentially 'druggable' mutations.
Conclusions:
- Next-generation sequencing is a sensitive and cost-effective method for screening oncogenes and tumor suppressors in ES.
- The identified mutations contribute to understanding ES pathogenesis.
- Findings support the development of personalized therapeutic strategies for ES patients based on their genetic profiles.
