TGFB1 and neoplasm: SMAD genes are key mediators of transforming growth factor β (TGF-β) signals that, on inactivation, enhance tumor growth.51,52 Previous studies have reported that SMAD3 variations are infrequent in CRCs (<5% of sporadic tumors and colorectal liver metastases).51,53,54,55 Consistent with these reports, we observed SMAD3 variations in fewer than 5% of AC cases.