SMAD4 and neoplasm: However, despite the increasing precision and depth of coverage, the four main driver genes identified before the time of next-generation sequencing (NGS) remain on the forefront: the oncogene KRAS, which is mutated in almost 95% of PDACs together with alterations of the tumor-suppressor genes CDKN2A, TP53 and SMAD4 [9,16,17].