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| Cells from metastasized Ewing's sarcoma. Source: Plos Biology |
Ewing's tumor is a rare form of bone cancer that occurs in children, adolescents and young adults. Dr. Olivier Delattre, Inserm research director, is a specialist of this tumor. Along with his team at Institut Curie, he has been working for many years on the differences in incidence of this tumor depending on the geographic origin. They have also collaborated with Gilles Thomas from the Synergie Lyon Cancer platform and David Cox, who are two researchers working at the Léon Bérard Center (Lyon) on this issue.
Most Ewing's tumors affect children of European origin and very seldom African and Asian populations. In addition, the number of cases in the latter two populations stays low even after migration in the United States (0.017 for 105 African-American individuals). “As a consequence, environmental factors could not be held responsible and the reasons behind the difference had to be found in the genome”, explained Olivier Delattre.
Such a genetic study, on a rare form of tumor, was made possible thanks to the development of new tools, in particular GWAS (Genome Wide Association Study), that enable the mapping of individual genetic variations. The analysis was performed on 401 Ewing's tumor samples, 684 control samples in the French population and 3,668 in the American population of European origin. Among over 700,000 observed genetic variations, two of them (rs9430161 and rs224278) are associated to the development of Ewing's tumor. “The risk is twice higher to develop Ewing's tumors for children baring the genetic variants than for the others”, explained David Cox. This increase in the relative risk is important to get a better understanding of the disease, but it has no consequence for those who harbor the variants since the absolute risk is very low, at approximately 3 cases per million of bearers of the variant. And these two genetic variants are a lot less frequent among populations of African and Asian origins, partially explaining the low incidence of the disease in these populations.
A better understanding of tumor development
In addition to the identification of the two susceptibility variants, this discovery improves our understanding of the cell mechanisms leading to the development of Ewing's tumors. The two identified regions are located next to the TARDBP and EGR2 genes. Similarities exist between TARDBP and the gene whose alteration is the origin of Ewing's tumors. And EGR2 belongs to a group of genes regulated by the EWS-FLI-1 fusion gene, who is responsible for this tumor. ”Henceforth, we will have the possibility to try to understand how the two genes increase the effect of the EWS-FLI-1 chromosomal abnormality that is responsible for Ewing's tumor”, added Olivier Delattre.
• With close to 100 new cases each year in France, Ewing's tumor is the second most frequent primitive
malignant tumor of the bones.
• It affects children, adolescents and young adults (under 30), with a peak of frequency at puberty. Also
called Ewing's sarcoma, it develops most commonly in the pelvis bones, the ribs, the thighs, the fibula and
the shinbones.
• Initially relying mainly on radiotherapy, treatment has significantly evolved in the past 30 years. Today,
localized forms are mainly treated using a combination of chemotherapy and surgery. Postoperative surgery,
and sometimes radiotherapy, complete the treatment. The prognosis of Ewing's tumor has benefited from
new chemotherapies
Source: Institut Curie Foundation