Aberrant expression of TRIM24 induces EMT and carcinosarcoma in vivo and correlates with worse overall survival of metaplastic breast cancer patients

Global profiling of tumor expression revealed increased RING-PHD-Bromodomain protein TRIM24 levels in numerous human cancers. Conditional over-expression of Trim24 was sufficient to drive murine mammary tumor development, 70% of which were ER, PR and HER2-negative carcinosarcomas with coexisting malignant epithelial and mesenchymal compartments, offering a unique model of human triple-negative, metaplastic breast cancer (MpBC). Both in vivo and in cellulo, TRIM24 induced EMT, repressing CDH1 and activating EMT factors. Whole exome sequencing of human MpBC tumors and Trim24-driven carcinosarcomas defined a TRIM24-like subclass of MpBC patients with worse overall and relapse-free survival. Among 40 MpBC patients, 43% had robust expression of TRIM24. These studies implicate TRIM24 as a potential biomarker and therapeutic target for a subset of MpBC.