Less than 10% eventually, and over the years, will pick up subsequent inactivating mutations in other tumour suppressor genes such as TP53 phosphatase and tensin homolog (PTEN), mothers against decapentaplegic homolog 4 (SMAD4) as well as oncogenic mutations, e.g., Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatidylinositol-4,5- bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA). This evidence concerns the gene SMAD4 and neoplasm.