Ewsr1, also known as Ewing sarcoma breakpoint region 1, is a gene with significant importance in various biological processes. It has been shown to play a role in maintaining centromere identity as it interacts with CENP-A and is required for keeping CENP-A at the centromere in interphase cells. Ewsr1 binds to CENP-A through the SYGQ2 region within the prion-like domain and to R-loops via its RNA-recognition motif, which are essential for maintaining centromere identity [2].

EWSR1 is the most frequently rearranged gene in mesenchymal neoplasia. Its chimeric oncoproteins drive a wide variety of neoplasms. For example, EWSR1 fusions with CREB family members (such as ATF1 and CREB1), as well as fusions in emerging entities like mesenchymal neoplasms with EWSR1::PATZ1 and EWSR1::NFATC2, are involved in tumorigenesis [1]. EWSR1-SMAD3 rearranged fibroblastic tumor is a recently characterized neoplasm with distinct clinicopathologic features and a recurrent EWSR1-SMAD3 gene fusion [3,4]. EWSR1::ATF1 translocation is a common tumor driver for distinct human neoplasms [5].

In conclusion, Ewsr1 is crucial for maintaining centromere identity. Its rearrangements, especially in mesenchymal neoplasia, play a significant role in tumor development. Understanding Ewsr1 through genetic models can provide insights into the mechanisms of neoplasm formation, potentially leading to new strategies for cancer treatment.