SMAD4 and colorectal carcinoma: Analogously, the prevalence of SMAD4 mutations in our cohort of patients was the same as that already reported for CRC (10%).18 This gene is a major contributor to CRC tumorigenesis and mutations in this gene are considered an adverse prognostic marker, as confirmed by our data showing a significantly shorter OS in two patients bearing the SMAD4 p.R361H mutation.