Pharmacologic Inhibition of Epigenetic Modification Reveals Targets of Aberrant Promoter Methylation in Ewing Sarcoma

Background: Ewing sarcoma, a highly aggressive tumor of children and young adults, is characterized most commonly by an 11;22 chromosomal translocation that fuses EWSR1 located at 22q12 with FLI1, coding for a member of the ETS family of transcription factors. Although genetic changes in Ewing sarcoma have been extensively researched, our understanding of the role of epigenetic modifications in this neoplasm is limited. Procedure: In an effort to improve our knowledge in the role of epigenetic changes in Ewing sarcoma we evaluated the in vitro antineoplastic effect of the DNA methyltransferase inhibitor 5-Aza-deoxycytidine (5-Aza-dC) and identified epigenetically silenced genes by pharmacologic unmasking of DNA methylation coupled with genome-wide expression profiling.