SMAD4 and invasive carcinoma: In support of our hypothesis, 14 of 38 (37%) of adenomas and adenocarcinomas had a single copy loss at the gene level of Smad4 (Fig. 5C), with Smad4 inactivation (by single-gene copy loss, aneuploidy, or prioritized mutation) occurring more often in invasive carcinomas versus adenomas [14 of 28 (50%) vs. one of 10 (10%), OR = 8.5, one-sided Fisher exact P = 0.03].