Tumor Type

Bone Cancer - Ewing sarcoma
Information on Ewing sarcoma and epidemiological characteristics can be found at http://genewing.curie.fr   HTML
Project Profile
Funding Organizations
Research Organizations
Research Activities
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Clinic & Pathology

France: Groupe Sarcome Français - Groupe d'Etudes des Tumeurs Osseuses (GSF-GETO)
Institut Curie
Institut Gustave Roussy
Institut National de la Santé et de la Recherche Médicale (INSERM)
Société Francaise des Cancers de l'Enfant (SFCE)
Spain: Centro Nacional de Análisis Genómico

The frequency of Ewing sarcoma is not even across human populations. It is mainly observed in population of European origin, extremely rare in population of African descent and intermediary in Asian populations. This striking epidemiological profile could be recently investigated by a GWAS which retrieved three loci on chromosome 1, 10 and 15 that demonstrated highly significant association with odds ratio and usually high for a cancer GWAS.

Clinically, the survival of ES patients has considerably beneficiated from the chemotherapy and radiotherapy. Nowadays, with the combination of chemotherapy followed by local control with a surgery and/or radiotherapy, cure rates of approximately 75% can be obtained in patient with localized disease. However the prognosis of patients with metastasis at diagnosis or with metastatic relapse remains very poor. Many laboratories worldwide have attempted to identify prognostic markers and new therapeutic targets. In terms of prognostic markers, genome wide analyses of copy number and/or of expression patterns as well as targeted resequencing of key cancer genes have enabled to identify genetic abnormalities that are of prognostic significance. These mainly include INK4A deletion, p53 mutations, increased copy number of chromosome 8 as well as expression levels of some genes have been associated with adverse prognosis. Yet none of those markers are presently sufficiently frequent or reliable to influence clinical management. Concerning therapeutic perspectives, Ewing cells are characterized by an activated IGF1 signaling pathway. Some remarkable responses using IGF1 inhibitors have been obtained in ES, yet these responses were rapidly followed by escape to this therapy. Recently, PARP inhibitors have been shown to have a remarkable efficiency in Ewing cell lines and small molecules blocking EWS/FLI-1 interaction with RNA helicase A have shown promising effect.

Sequencing & Analysis

France: NGS Core Facility - Institut Curie
Spain: Centro Nacional de Análisis Genómico

Whole Genome Analysis are currently being performed on Illumina HiSeq 2000 sequencing machines at the CNAG in Barcelona and at the St Jude in Memphis.

RNASeq Analysis are performed on Illumina HiSeq 2000 sequencing machines at the Curie institute in Paris.

Complementary Studies

France: INSERM U830

The “genetics and biology of pediatric tumor group” focused on three types of childhood cancers including Ewing sarcoma, neuroblastoma and rhabdoid tumors. In Ewing sarcoma, main projects include the study of EWS-FLI1 mechanisms of action and the search for somatic or germline genetic variants that may cooperate with EWS-FLI1 in oncogenesis. Large collections of Ewing sarcoma have been profiled by expression arrays and CGH and various models are available for follow-up studies.

Data Storage, Analysis & Management

France: Bioinformatic Unit - Institut Curie
Spain: Centro Nacional de Análisis Genómico

Details to follow

Project Publications
Project Summary

Ewing sarcoma (ES) is the second most common primary malignant Soft Tissue tumour in children and adolescent after osteosarcoma. The annual incidence is approximately 3 per million with a slight male predominance. The mean age at diagnosis is 15 years. It can affect all Soft Tissues with the most common primary site being pelvis, femur and tibia. It can also arise in soft tissue in approximately 10% of cases.

Histologically ES belongs to the group of small blue round cells tumours in children with two characteristics that are not absolutely specific: abundant cytosplamic glycogene and strong cell membrane expression of CD99.
Genetically, ES is characterized by gene fusions linking members of the TET family of RNA binding encoding genes (mainly EWSR1) to ETS family members, usually FLI-1. The chimeric genes are potent oncogenes that can transform NIH3T3 cells and that are thought to mainly act through inappropriate regulation of specific target genes. The involvement of the chimeric proteins in the regulation of splicing has also been suggested.

The goal of the project is to establish the catalogue of somatic mutations that may cooperate with EWS-ETS fusion in the development of the tumor. The Ewing’s sarcoma project aims to perform 100 whole genome sequencing of germline and tumor DNA as well as at least 50 RNA-seq from tumors. Correlations between molecular profiles and clinical features will be established. The mutated genes will be further validated in a series of 500 ES from our Tumor Bank.

Principal Investigators

• Olivier Delattre

Lead Jurisdiction