Small molecular inhibitors, such as MIs, nutlins, and RITA, have been tested as therapeutic agents in CRC by activating this pathway.23 In addition to SMAD4, we identified a novel mutation in TGFBR2 (p.D549A) and ATM (p.E650*) (Figure S1M,N). The gene discussed is SMAD4; the disease is colorectal carcinoma.