SMAD4 and metastatic neoplasm: Furthermore, when the heterogeneity score data was analysed separately for trunk drivers (APC, RAS-BRAF), branching driver (TP53) and other (PIK3CA, SMAD4, CDH1, etc.)mutations, only the RAS-BRAF somatic mutations showed significant but poor correlation between primary and metastatic tumours (r = 0.588, r2 = 0.346, P = 0.035) (Fig. 1b).