Ewing sarcoma (ES) is a rare but deadly bone tumor which occurs mainly in adolescents and young adults.1 As survival for ES has not improved beyond ~60% in the last few decades, it is critical to enable the prediction and early detection of disease through the discovery of genetic contributions to risk. While the literature on the causes of ES is sparse, several lines of evidence have emerged which collectively suggest that de novo germline mutations (DNM's) underlie a proportion of cases. These include a lack of environmental risk factors or syndromes associated with ES and a strong increasing risk with rising parental age. Given the strong rationale for examining DNMs in ES, we propose the following specific aims using WGS data of germline from 331 case-parent trios: 1) to identify germline DNMs in ES patient genomes; 2) to identify regions with recurrent DNMs in ES patient genomes; and 3) to compare the burden of pathogenic variation from DNMs or otherwise in an extended set of 457 ES patients with WGS data to controls. The analysis will be the definitive examination of DNMs in ES. Results indicating DNMs are a frequent cause of ES could lead to clinical guidelines urging sequencing of all patients, who currently receive little genetic testing due to lack of family history. Lastly the results could potentially point to opportunities for early detection and possibly therapeutic targets.

Public Health Relevance

Ewing sarcoma (ES) is a rare but deadly bone cancer that occurs mainly in adolescents and young adults. Although only about 300 cases of ES occur in the United States each year, survival is low at about 60%; by identifying genes and loci associated with ES risk we may improve early detection of ES and discover possible therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA218733-02
Application #
9660536
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Daee, Danielle L
Project Start
2018-03-05
Project End
2020-02-29
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455