SMAD4 and neoplasm: Since tumor progression and spatial separation of tumor subclones support parallel evolution, i.e., different subclones evolving in parallel acquire distinct mutations in the same gene (e.g., SMAD4) and/or pathway (e.g., TGFβ-pathway), we next sought our data set for further evidence of parallel evolution: 369 genes of our discovery cohort harbored two to four different non-synonymous mutations in the same patient (Additional file 2: Table S10), some of which could be due to parallel evolution.