Schiffman Lab - Ewing Sarcoma

What is Ewing Sarcoma?

Ewing Sarcoma is the second most common bone cancer in children and young adults. In addition to bone, Ewing tumors can also arise in soft tissue. Overall, Ewing Sarcoma affects one in 1 million people in the United States and is most common in individuals aged 10 to 19. Ewing Sarcoma is driven by a type of genetic change called a translocation.

Translocations and the Development of Ewing Sarcoma

A translocation occurs when two pieces of DNA in our cells that are normally separated become fused together. In Ewing Sarcoma, the two pieces of the genome that become fused involve a gene called EWSR1 and another gene in the ETS family of transcription factors.

Approximately 85% of patients have a translocation called EWS-FLI. This means that EWSR1 is fused to another gene called FLI1. The combination of EWSR1 with FLI1 (or other ETS transcription factors) creates a fusion protein that is believed to promote the development of Ewing Sarcoma by activating genes responsible for cell proliferation and tumorigenesis. It is still unclear exactly what causes these translocations to occur or how fusion proteins like EWS-FLI lead to the development Ewing Sarcoma. These are some of the questions that we hope to answer in our research.

The current survival rates for Ewing’s Sarcoma are 60% for localized disease, less than 20% for metastatic disease, and as low as 10% for relapsed patients. More work is needed in order to help improve the outcomes for patients and families affected by this disease. In the Schiffman Lab, we believe that a better understanding of the genetic origins of Ewing Sarcoma may lead to new strategies to one day treat, or even prevent, disease in patients.

Genetic Predispositions for Ewing Sarcoma

Project GenESis (Genetics of Ewing’s Sarcoma International Study)

The aim of our Ewing Sarcoma research projects is to gain a better understanding of the genetic origins of the disease, with the hope of finding more effective ways for treatment and prevention. The current genetic and epidemiological evidence suggests that there may be a component of genetic predisposition for Ewing Sarcoma, but it is not yet clear what this might be. Project GenESis is an international study that aims to identify the DNA sequences or changes that increase the chances of someone developing Ewing Sarcoma. Our approach involves sequencing the DNA of participants with Ewing Sarcoma as well as conducting laboratory experiments on normal and tumor DNA from patients with Ewing sarcoma. We also collect family pedigrees and medical histories to identify patterns in the genetic inheritance of phenotypes (the physical manifestations of genes) associated with Ewing Sarcoma. If a genetic predisposition is identified, this could lead to improvements in screening and survival for Ewing Sarcoma patients.

Find out more about how you can participate.

Gabriella Miller Kids First (GMKF) Partnership

The Gabriella Miller Kids First Pediatric Data Resource is a NIH-funded resource to compile genetic sequencing data for pediatric research. Funding from Kids First has allowed us to perform whole-genome sequencing on over 300 Ewing’s Sarcoma patients from Project GenESis and their parents. Thanks to this partnership, we are analyzing over 1,000 whole genome sequences for Project GenESis in hopes of being able to identify the genetic factors that contribute to Ewing Sarcoma development. Our lab was just awarded a second grant from the GMKF program to expand this analysis to look at the genomic changes in tumors from patients with Ewing sarcoma, and to see how these related to any possible inherited risk for this rare tumor.

The Genetics of Ewing’s Sarcoma Tumors

Tumor Genomics

In addition to studying the genes in normal DNA that contribute to the development of Ewing Sarcoma, we also study the genetics of Ewing Sarcoma tumors. Tumors harbor genetic mutations in their DNA that are usually not found in healthy tissue. Some of our projects are dedicated to finding these genetic differences and elucidating their functions, including the unique biological pathways they affect. Through this, we hope to understand more about the role they may play in maintaining the Ewing Sarcoma phenotype, so that we can identify potential targets for treatment and better predict outcomes for Ewing Sarcoma patients.  We are very interested in looking at copy number changes in the tumors of patients with Ewing Sarcoma, as well as specific genes like CEBPb that promote the formation of Ewing Sarcoma cell colonies and chemotherapy resistance. We are excited to continue our work linking both the germline and tumor genomics of this disease to help patients with Ewing Sarcoma.

Joshua Schiffman, MD

Principal Investigator

joshua.schiffman@hci.utah.edu
Cancer Center Bio

Contact Us

For any and all questions, or to find out how you can get involved, please email Schiffman.Research@hci.utah.edu

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