Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.

Ewing Sarcoma (ES) is an aggressive, mesenchymal malignancy associated with a poor prognosis in the recurrent or metastatic setting with an estimated overall survival (OS) of <30% at 5 years. ES is characterized by a balanced, reciprocal chromosomal translocation involving the RNA-binding protein and transcription factor gene ( being the most common). Interestingly, murine ES models have failed to produce tumors phenotypically representative of ES. Genomic alterations (GA) in ES are infrequent and may work synergistically with translocations to promote oncogenesis. Aberrations in fibroblast growth factor receptor (), a receptor tyrosine kinase (RTK) have been shown to contribute to carcinogenesis. Mouse embryonic fibroblasts (MEFs) derived from knock-in strain of homologous mice display a transformed phenotype with enhanced TGF-induced mammary carcinogenesis. The association between the SNV in high-grade soft tissue sarcomas has previously been demonstrated conferring a statistically significant association with poorer OS. How the SNV specifically relates to ES has not previously been delineated. To further define the genomic landscape and corresponding pathway alterations in ES, comprehensive genomic profiling (CGP) was performed on the tumors of 189 ES patients. The SNV was identified in a significant proportion of the evaluable cases ( = 97, 51%). In line with previous analyses, ( = 36, 19%), ( = 33, 17%), and ( = 22, 11.6%) represented the most frequent alterations in our cohort. Co-occurrence of and alterations was observed ( = 5, 3%). Notably, we identified a higher proportion of mutations than previously observed. The most frequent pathway alterations affected ( = 89, 24% of pathological samples), ( = 75, 25%), ( = 69, 23%), Histone/Chromatin remodeling ( = 57, 24%), and ( = 64, 20%). These findings help to further elucidate the genomic landscape of ES with a novel investigation of the SNV revealing frequent aberration.