Ewing sarcoma – an enhancer disease?

Cancer is a leading cause of death among children in the developed world. Advances in research and treatment have raised survival rate to 80% and above for many childhood cancers. However, there are still a number of rare cancers that are very aggressive and difficult to treat with existing therapies. The recent discovery of epigenetic defects in some of these childhood cancers these are changes in the way the DNA is packaged within a cell provide interesting new angles for cancer research because epigenetic defects are in principle reversible using epigenetic drugs. In our previous work, we showed that Ewing sarcoma cells carry many epigenetic defects, and we identified alterations in enhancers (these are regions that control the activity of genes) as an important mechanism in this cancer type. In the current project, we will investigate the hypothesis that Ewing sarcoma is an enhancer disease, which could identify promising new routes toward developing therapies for this deadly cancer. The project Ewing sarcoma an enhancer disease? will be conducted in the laboratory of Professor Heinrich Kovar at the St. Anna Childrens Cancer Research Institute (CCRI) in Vienna, Austria. The CCRI is Austrias leading center for research related to childhood cancer and affiliated with the Medical University of Vienna. The planned work will involve collaborations with leading cancer researchers in Austria, France, and the UK.

Cancer is a leading cause of death among children in the developed world. Advances in research and treatment have raised survival rate to 80% and above for many childhood cancers. However, there are still a number of rare cancers that are very aggressive and difficult to treat with existing therapies. The recent discovery of epigenetic defects in some of these childhood cancers (with "epigenetic", we refer to changes in the way the chromatin is organized and DNA is packaged within a cell) provide interesting new angles for cancer research, part because epigenetic defects may be reversible using epigenetic drugs. We have previously showed that Ewing sarcoma cells carry widespread epigenetic changes, and we identified alterations in enhancers (i.e., genomic regions that control the activity of nearby genes) as an important mechanism in this cancer type. In this Elise Richter project, we investigated the hypothesis that Ewing sarcoma is an enhancer disease, and we found that epigenetic differences explain part of the clinical and phenotypic heterogeneity observed among patients with Ewing sarcoma. We have also developed a blood test for monitoring tumor-specific epigenetic defects using the liquid biopsy concept. The project "Ewing sarcoma - an enhancer disease?" was conducted in the laboratory of Eleni Tomazou at the St. Anna Children's Cancer Research Institute (CCRI) in Vienna, Austria. The CCRI is Austria's leading center for research related to childhood cancer. The successfully completed research involved collaborations with leading cancer researchers in Austria, France, Germany and the UK.