The hotspots include two AA residues, i.e. P305 and R321 mutated 3 and 4 times, respectively, and the nonsense mutation p.S464Ter truncating the protein by five AAs, which is the most common SMAD2 mutation (13 occurrences in cancers such as COAD, STAD, and BRCA). This evidence concerns the gene SMAD2 and cancer.