After performing translocation site analysis using target region sequencing data in two Xp11.2 tRCC cell lines and ten Xp11.2 tRCC patients, we confirmed that TOP2β and ERα could both bind to TFE3 translocation sites directly to mediate DNA breaks in a E2-dependent manner. The gene discussed is TOP2B; the disease is renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.