The first alteration is associated with a global loss of receptor signaling, resulting in a reduction in the tumor suppressive activity of TGF-β1, whereas the second is associated with overproduction of bioactive TGF-β1, resulting in the activation of a pro-invasive, -angiogenic and -metastatic TGF-β1-regulated gene expression program, thus inducing a tumor cell phenotype that is mesenchymal and highly metastatic (11). The gene discussed is TGFB1; the disease is neoplasm.