We have initially proposed that oncogenic transformation may have a role in triggering cancer coagulopathy.58 Indeed, molecular aberrations (mutations) driving human cancers possess unique molecular features and phenotypic consequences,59 and so could their impact on the ability of tumor cells to interact with the coagulation system.43 Driver mutations alter or abolish the function of specific genes acting as tumor suppressors (e.g. PTEN, TP53, SMAD4) or result in activation of proto-oncogenes (RAS, MYC, MET, EGFR). Here, SMAD4 is linked to cancer.