SMAD4 and adenoma: Combined, exome-wide studies of conventional adenomas reveal that APC, KRAS, PIK3CA, TP53 and SMAD4 genes affecting Wnt, RAS, PI3K, p53 and TGF-beta signaling pathways are amongst those most commonly altered, often with significantly increasing mutation prevalence in development from non-advanced conventional adenomas to advanced conventional adenomas to CRC [23,24,25,26,27,28].