Moreover, targeted sequencing of available gene panels has revealed high mutational consistency for key cancer-associated and driver genes, as for example KRAS, NRAS, BRAF, APC, PIK3CA and SMAD4, suggesting that driver events occur early in evolution and that a single biopsy of either tumor possibly accurately recapitulates the cancer mutational landscape for drivers of tumorigenesis [57,58,59]. Here, SMAD4 is linked to cancer.