SMAD4 and neoplasm: Mutations or deletions in SMAD4, CDKN2A, TP53, PIK3CA, and/or PTEN are associated with advanced neoplasia; more specifically, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN have been reported to have an 89% sensitivity and 100% specificity for advanced neoplasia [46].