Germline Variation and Somatic Alterations in Ewing Sarcoma

Ewing sarcoma (EwS) is a rare bone or soft tissue tumor that occurs early in life, suggesting genetic variation is likely a major contributor to EwS risk. To date, genetic investigations have identified key somatic mutations and germline variants of importance for EwS risk. While substantial progress has been made in uncovering the genetic etiology of EwS, considerable gaps in knowledge remain. Herein, we provide a summary of methodological approaches for future genomic investigations of EwS. We anticipate that this recommended analytical framework for germline and somatic investigations, along with genomic data from growing EwS case series, will aid in accelerating new genomic discoveries in EwS and expand knowledge of the genetic architecture of this aggressive sarcoma.