Fig. 8: Model on cell context dependency of ERG oncogenicity.
From: ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L
ERG translocations (in the context of PTEN loss) that occur in a subset of basal cells with luminal transcriptomic features (BasalLum cells) enter a highly proliferative multi-lineage IM state that, in turn, drives invasive cancer with luminal differentiation. By contrast, ERG translocations that originate in luminal cells may develop intraductal hyperplasia but fail to progress to invasive cancer. The basal-derived IM cells provide a chromatin context to support maximal ERG-driven chromatin changes, featuring TFs (NF-κB, AP-1, NFAT, STAT) in addition to ERG and epigenetic regulators (MLL1, DOT1L).
