SMAD4 and carcinoma: Studies have associated non-hypermutated, microsatellite stable (MSS) CIN with common recurrent mutations in APC (81%), TP53 (60%), KRAS (43%), SMAD4 (10%), PIK3CA (18%), NRAS (9%) etc. CIN tumors usually arise as a consequence of a combination of oncogene activation (e.g. KRAS, PIK3CA) and tumor suppressor gene inactivation (e.g. APC, SMAD4 and TP53) by allelic loss and mutation, which go along with changes in tumor characteristics in the adenoma to carcinoma sequence[6].