EWSR1 and cancer: In summary, reactivation of pericentromeric heterochromatin in cancers with aberrantly expressed ETS proteins, including EWS:FLI1 and ERG, results in expression and dissemination of HSAT2,3 RNAs, which, together with HERV-K and other retroelement RNAs present in EVs, may activate DNA damage and cGAS-pTBK innate immune signaling in the recipient immune cells and fibroblasts, driving local and systemic inflammation (Figure 7G).