Many hematopoietic malignancies have oncogenic gene fusions, like BCR-ABL, in their tumor-initiating cells. This implicates the product of the fusion as a powerful cancer-initiating event. In human prostate cancers, despite the detection of numerous similar fusions, e.g., the TMPRSS2-ERG fusion, there was no evidence for its presence in the root of the cancer, the cancer stem cells. Polson et al. now not only report that the fusion is indeed present and active in tumor initiating cells from human prostate cancers, but that its expression is tightly controlled by epigenetic mechanisms, with potential impacts on tumor latency and treatment.

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