Indeed, in LUAD, the majority of frequently mutated cancer genes (22 out of 40) were subject to significant positive subclonal selection (adjusted ratio of non-synonymous to synonymous mutations (dN/dS) lower, 95% confidence interval (CI) of >1), including PIK3CA, RB1 and SMARCA4. In 7 out of 22 of these genes, including HIST1H1C, KMT2D, PTEN, RUNX1 and SMAD4, no significant positive selection was detectable in truncal mutations. Here, SMARCA4 is linked to cancer.