Five domain instances were found to be significantly mutated in more than one cancer (Table 4): a Ras domain instance of KRAS, mutated in lung and pancreatic cancer; a PHD finger domain instance (zf-HC5HC2H) of MLL3, mutated in breast and prostate cancer; a MAD homology 2 (MH2) domain instance of SMAD4, mutated in colon and esophageal cancer; a SNF2 family N-terminal (SNF2_N) domain instance of SMARCA4, mutated in esophageal cancer and cancer of the central nervous system; and the P53 DNA binding domain instance of TP53, mutated in 8 cancer types. Here, SMAD4 is linked to familial pancreatic carcinoma.