Our finding that disruption of 3 or 4 TP53 and PTEN alleles in untreated prostate tumors serves as a causative factor in an activated TGF-β transcriptional signature is consistent with proposed models in which TGF-β can either directly activate AKT independent of SMADs to promote proliferation or alternatively cooperate with TP53 loss to re-engage developmental pathways, including EMT, to facilitate metastasis [22–24]. The gene discussed is PTEN; the disease is prostate neoplasm.