Among the mutations acquired before the emergence of the most-recent common ancestor are several in cancer genes, including TP53, PIK3CA, GATA3, MLL3, SMAD4, and NCOR1. In addition, the trisomy 1q described above had occurred, as well as an unbalanced t(1;22) translocation and a cluster of chromothripsis rearrangements involving chromosomes 2, 4, 18, and 21 (Figure S2E). Here, SMAD4 is linked to cancer.