Description
Olivia Lee, BS, and Mitchell Machiela, ScD, MPH, will discuss their long-read sequencing investigation of the 6p25.1 Ewing sarcoma susceptibility locus. Their investigation identified that longer variants in a GGAA microsatellite are associated with increased Ewing sarcoma risk by promoting EWSR1-FLI1 binding and altering transcription of nearby RREB1.
Overview of Presentation
• Germline variation at 6p25.1 leads to increased Ewing sarcoma susceptibility
• The 6p25.1 susceptibility locus includes a GGAA microsatellite that is bound by EWSR1-FLI1, a frequent translocation occurring in Ewing sarcoma cases
• Longer alleles of the GGAA microsatellite generally promote better EWSR1-FLI1 binding and were associated with increased Ewing sarcoma risk.
• Functional investigation of the GGAA microsatellite implicate de novo enhancer activity that alters RREB1 expression.
