The Genomic Landscape of Pediatric Ewing Sarcoma

Abstract

We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma.

Transgenic antigen-specific, HLA-A*02:01-allo-restricted cytotoxic T cells recognize tumor-associated target antigen STEAP1 with high specificity

“…[25][26][27][28] However, the addition of adjunctive, immune-activating therapies during first remission demonstrated the potential to reduce recurrence rates and exploit immunotherapy approaches for ES patients. 29 Balanced chromosomal EWS/ETS translocations that give rise to oncogenic chimeric proteins (EWS-ETS), the most common being EWS-FLI1 as a consequence of the t(11;22)(q24; q12) translocation, 30,31 are the characteristic driver event of ES tumorgenesis.…”

Cruel fusion: What a young man’s death means for childhood cancer

“…Instead, three different teams found the same result: Ewing's sarcomas always contained a fusion protein, most often but not always EWS-FLI1, and little else [4][5][6] . There were no other potential…”

Ewing sarcoma partial regression without GvHD by chondromodulin-I/HLA-A*02:01-specific allorestricted T cell receptor transgenic T cells

“…[9][10][11]26,27 Since oncogenic drivers often are not antigenic, additional targets selectively overexpressed and required for malignancy and metastasis are to be identified supporting the application of TCR driven T cells. 15,28,29 CHM1 is directly upregulated by the ES driving fusion oncogene EWS-FLI1 and maintains an undifferentiated, invasive phenotype, and metastatic spread. Given its critical role in ES malignancy, CHM1 constitutes an excellent therapeutic target.…”