TGFB1 and adenoma: Subsequent mutational events in humans are selected for during the progression of adenoma to invasive and metastatic carcinoma, e.g. RAS/MAPK GOF, PTEN and TP53 LOF, and later acquired LOF mutation of the TGF-β-BMP ligand activated receptor pathway, such a mutation of receptors and Smad2/3/423.