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.
Highlights
Ewing sarcoma (ES) is an aggressive and poorly differentiated tumor of the bone or soft tissues
The study was approved by the Human Research Ethics Committee of Peking University, Beijing, China. 20 archived FFPE ES specimens were obtained from the Department of Pathology in Peking University Third Hospital, and the institutional ethics committee waived the need for informed consent
A total of 20 ES patients were involved in the current study (Table 1)
Summary
Ewing sarcoma (ES) is an aggressive and poorly differentiated tumor of the bone or soft tissues. It preferentially occurs in children and young adults, with a peak occurrence at an age of 15 years [1]. The five-year survival rate for localized disease is approximately 70%, but the overall survival of patients with metastatic or relapsed disease is lower than 30% [2,3]. Few drugs, including intensified chemotherapeutics, are available for the treatment of ES patients with metastatic disease. PLOS ONE | DOI:10.1371/journal.pone.0153546 April 14, 2016
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