Remarkably, SFPQ-TFE3 expression is sufficient to induce lineage plasticity, with down-regulation of the PAX2/PAX8 nephric lineage factors and tubular epithelial markers, and up-regulation of PEComa differentiation markers in transgenic mice, cell lines and human tRCC. This evidence concerns the gene PAX2 and renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.